chr11-5226774-G-A

Variant names:

Variant summary

Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong

The NM_000518.5(HBB):c.118C>T(p.Gln40*) variant causes a stop gained change. The variant allele was found at a frequency of 0.000157 in 1,614,132 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

HBB
NM_000518.5 stop_gained

Scores

Clinical Significance

Pathogenic criteria provided, multiple submitters, no conflicts P:39O:1

Conservation

PhyloP100: 3.64

Variant links:

Genes affected

HBB (HGNC:4827): (hemoglobin subunit beta) The alpha (HBA) and beta (HBB) loci determine the structure of the 2 types of polypeptide chains in adult hemoglobin, Hb A. The normal adult hemoglobin tetramer consists of two alpha chains and two beta chains. Mutant beta globin causes sickle cell anemia. Absence of beta chain causes beta-zero-thalassemia. Reduced amounts of detectable beta globin causes beta-plus-thalassemia. The order of the genes in the beta-globin cluster is 5'-epsilon -- gamma-G -- gamma-A -- delta -- beta--3'. [provided by RefSeq, Jul 2008]

HBB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 18 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. There are 110 pathogenic variants in the truncated region.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 11-5226774-G-A is Pathogenic according to our data. Variant chr11-5226774-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 15402.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-5226774-G-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HBB	NM_000518.5 link	c.118C>T	p.Gln40*	stop_gained	Exon 2 of 3	ENST00000335295.4	NP_000509.1	P68871D9YZU5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HBB	ENST00000335295.4 link	c.118C>T	p.Gln40*	stop_gained	Exon 2 of 3	1	NM_000518.5	ENSP00000333994.3		P68871

Frequencies

GnomAD3 genomes

AF:

0.000269

AC:

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000397

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.000330

AC:

AN:

251376

Hom.:

AF XY:

0.000368

AC XY:

AN XY:

135848

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000677

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000145

AC:

212

AN:

1461870

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

127

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000169

Gnomad4 OTH exome

AF:

0.000265

GnomAD4 genome

AF:

0.000276

AC:

AN:

152262

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000412

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.000285

Hom.:

Bravo

AF:

0.000230

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000420

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00202

EpiControl

AF:

0.00196

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:39Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

beta Thalassemia

Pathogenic:13Other:1

Apr 08, 2016

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant summary: The c.118C>T variant results in a premature termination codon, predicted to cause a truncated or absent HBB protein, which is a commonly known diease mechanism in hemoglobinopathy. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.217dupA, c.230delC, c.251delG, etc. ). This variant is found in 51/121354 control chromosomes at a frequency of 0.0004203, which does not exceed maximal expected frequency of a pathogenic allele (0.0111803). This variant is a well-known common pathogenic variant in Sardinian and other populations (Danjou_2012, Sirdah_2013). Multiple reputable databases classified this variant as pathogenic. Taken together, this variant has been classified as pathogenic. -

Feb 11, 2016

HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: research

- -

Feb 10, 2016

Baylor Genetics

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

Our laboratory reported dual molecular diagnoses in HBB (NM_000518.4, c.118C>T) and KANSL1 (NM_001193466.1, c.985_995del) in one individual with reported features of delayed motor milestones, delayed speech, intellectual disability, dysmorphic features, familial short stature, minor beta-thalassemia, eye anomalies (strabismus, nearsighted) and cafe au lait spot on right upper chest. Brain MRI showed asymmetric prominent ventricles, possible undermyelination and amygdalo/hippocampal dysgenesis. The same variant has been found in 4 additional individuals with beta thalassemia trait. -

GeneReviews

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

- -

Feb 17, 2022

Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PVS1, PS3, PM3 -

Nov 25, 2019

The ITHANET community portal, The Cyprus Institute of Neurology and Genetics

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: curation

- -

Sep 16, 2020

Natera, Inc.

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Dec 10, 2019

Myriad Genetics, Inc.

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

NM_000518.4(HBB):c.118C>T(Q40*) is classified as pathogenic in the context of Hb beta chain-related hemoglobinopathy. Please note that Q40* is associated with beta thalassemia and is classified as a beta-zero variant. Sources cited for classification include the following: PMID 1734721 and 21417574. Classification of NM_000518.4(HBB):c.118C>T(Q40*) is based on the following criteria: The variant causes a premature termination codon that is expected to be targeted by nonsense-mediated mRNA decay and is reported in individuals with the relevant phenotype. Please note: this variant was assessed in the context of healthy population screening. -

Jul 22, 2021

Genome-Nilou Lab

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 15, 2016

Genetic Services Laboratory, University of Chicago

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 25, 2019

Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Mar 10, 2021

Institute of Human Genetics, University of Leipzig Medical Center

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 18, 2019

Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This nonsense variant found in exon 2 of 3 is predicted to result in loss of normal protein function. This variant has been previously reported in trans with a second HBB variant in individuals affected with with beta-thalassemia (PMID: 6457059, 23637309, 21417574, 27821015, 20301599). The variant was been classified as Pathogenic by multiple clinical laboratories in the ClinVar database (Variation ID: 15402). Functional studies of the variant using transfected Hela cells demonstrate significantly reduced mRNA expression with no protein detected, suggesting that the variant transcript undergoes nonsense-mediated mRNA decay (PMID: 21389146). It is present in the heterozygous state in the gnomAD population database at a frequency of 0.03% (87/282760). Based on the available evidence the c.118C>T (p.Gln40Ter) variant is classified as Pathogenic. -

Mar 20, 2024

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The p.Gln40X variant, also reported as p.Gln39X, in HBB is a well-known pathogenic variant that has been identified in the homozygous or compound heterozygous state with another pathogenic variant in >300 individuals with beta thalassemia (Rosatelli 1992 PMID: 1734721, Ghedira 2011 PMID: 21417574, Danjou 2012 PMID: 22271886, Sirdah 2013 PMID: 23321370, Herrera 2015 PMID: 25572186, Gallagher 2016 PMID: 27821015, Hussain 2017 PMID: 28670940, Carrocini 2017 PMID: 28366028). It has also been reported by other clinical laboratories in ClinVar (Variation ID 15402). Additionally, it has been identified in 0.02% (14/60012) of Admixed American and 0.02% (80/12912216/11800180) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org, v.4.0.0). However, this frequency is low enough to be consistent with a recessive carrier frequency. This nonsense variant leads to a premature termination codon at position 40 and has shown decreased mRNA expression level with no protein detected in p.Arg40X transfected Hela cells, suggesting that the variant undergoes nonsense-mediated mRNA decay (Neu-Yilik 2011 PMID: 21389146). Biallelic loss of function of the HBB gene is an established disease mechanism in autosomal recessive beta thalassemia. In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive beta thalassemia. ACMG/AMP Criteria applied: PVS1, PM3_VeryStrong, PM2_Supporting. -

not provided

Pathogenic:9

May 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

HBB: PM3:Very Strong, PVS1, PM2 -

Mar 30, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change creates a premature translational stop signal (p.Gln40*) in the HBB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in HBB are known to be pathogenic (PMID: 23637309). This variant is present in population databases (rs11549407, gnomAD 0.06%). This premature translational stop signal has been observed in individuals with beta-thalassemia (PMID: 8095930, 25572186, 27427187, 28366028). This variant is also known as p.Gln39X. ClinVar contains an entry for this variant (Variation ID: 15402). For these reasons, this variant has been classified as Pathogenic. -

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 26, 2021

Revvity Omics, Revvity

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 30, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The Codon 39 C>T variant (HBB c.118C>T; p.Gln40Ter, also known as Gln39Ter when numbered from the mature protein, rs11549407, HbVar ID: 845) induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. This variant is one of the most common Mediterranean beta(0) thalassemia variants (see HbVar link and references therein) and is considered to be pathogenic. References: Link to HbVar database: https://globin.bx.psu.edu/hbvar/menu.html -

Dec 01, 2020

Quest Diagnostics Nichols Institute San Juan Capistrano

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The HBB c.118C>T (p.Gln40*) variant causes the premature termination of beta-globin protein synthesis and is associated with beta-zero thalassemia (see HbVar (http://globin.cse.psu.edu/cgi-bin/hbvar/counter), and PMID: 6457059 (1981), 6985481 (1981), 6896219 (1982)). Previous names for this pathogenic variant include codon 39 (C>T) and Gln39X. -

Oct 19, 2017

Clinical Genetics and Genomics, Karolinska University Hospital

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 21, 2016

Eurofins Ntd Llc (ga)

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 20, 2022

GeneDx

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

One of the major beta-thalassemia alleles in the Mediterranean area (HbVar ID 845; Giardine et al., 2014); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Published functional studies demonstrate a damaging effect with significantly reduced mRNA expression level in R40X transfected Hela cells with no protein detected, suggesting that the variant transcript undergoes nonsense-mediated mRNA decay (Neu-Yilik et al., 2011); Identified in multiple individuals with beta-thalassemia minor or beta-thalassemia trait referred for genetic testing at GeneDx; Q40X has also been reported as Q39X using alternative nomenclature; This variant is associated with the following publications: (PMID: 2867271, 21417574, 25087612, 22975760, 1734721, 25572186, 21228398, 20301599, 6457059, 27821015, 8095930, 28670940, 27959697, 28366028, 24137000, 30665703, 31784700, 27427187, 32248411, 8103502, 34426522, 8195005, 1795494, 33326653, 31589614, 15609277, 9629495, 33339817, 9163586, 2577233, 21389146) -

Beta-thalassemia HBB/LCRB

Pathogenic:8

Feb 01, 2024

Laboratory of Medical Genetics, National & Kapodistrian University of Athens

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: curation

- -

Feb 23, 2023

3billion, Medical Genetics

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.031%). This variant was predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000015402 / PMID: 6457059). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. -

Jan 13, 2023

Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ACMG classification criteria: PVS1 very strong, PS4 strong -

Feb 03, 2020

Genetics and Molecular Pathology, SA Pathology

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 11, 2024

Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. 0102 - Loss of function is a known mechanism of disease in this gene and is associated with HBB-related hemoglobinopathies, including beta thalassemia (OMIM). Dominant negative is also a suggested mechanism (PMID: 29700171). (I) 0108 - This gene is associated with both recessive and dominant disease. (I) 0115 - Variants in this gene are known to have variable expressivity. Variable severity has been reported in sickle cell patients carrying the same variants (PMID: 31788855). In addition, clinical severity of beta-thalassemia patients is also dependent on whether variants in HBB are heterozygous, homozygous or compound heterozygous, and the amount of residual protein that is expressed (GeneReviews). (I) 0200 - Variant is predicted to result in a missense amino acid change from glutamic acid to lysine. (I) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD <0.01 (v2: 64 heterozygotes, 1 homozygote). (SP) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0600 - Variant is located in the annotated Hb-beta-like domain (NCBI). (I) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. Also known as p.(Glu26Lys) and the HbE variant, it has been identified in at least ten patients and is known as a pathogenic structural variant. (GeneReviews; ClinVar, PMID: 28546763). (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign -

May 24, 2022

MGZ Medical Genetics Center

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 17, 2023

Institute of Human Genetics, University of Leipzig Medical Center

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

_x000D_ Criteria applied: PVS1, PS3, PS4, PP4 -

Nov 24, 2023

Zotz-Klimas Genetics Lab, MVZ Zotz Klimas

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Hb SS disease

Pathogenic:2

Baylor Genetics

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 09, 2023

Illumina Laboratory Services, Illumina

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The HBB c.118C>T (p.Gln40Ter) nonsense variant, also referred to as p.Gln39Ter, results in the loss of normal protein function through nonsense-mediated mRNA decay. This variant is one of the commonly identified pathogenic variants in individuals with beta-thalassemia from the Mediterranean region, accounting for most cases in Sardinia (PMID: 23637309). The p.Gln40Ter variant has been reported in a homozygous or compound heterozygous state in more than 300 individuals with different forms of beta-thalassemia (PMID: 9163586; 22271886; 23321370; 27199182; 33000750). The frequency of this allele in the Genome Aggregation Database is 0.000655 in the Latino/Admixed American population (version 3.1.2). A functional study using HeLa cells showed reduced mRNA expression with no protein detected in cells transfected with the variant compared to wildtype, suggesting the variant undergoes nonsense mediated mRNA decay (PMID: 21389146). Based on the available evidence, the c.118C>T (p.Gln40Ter) variant is classified as pathogenic for sickle cell disease. -

Beta zero thalassemia

Pathogenic:1

Feb 01, 1992

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Inborn genetic diseases

Pathogenic:1

Dec 09, 2016

Ambry Genetics

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The p.Q40* pathogenic mutation (also known as c.118C>T and p.Q39X), located in coding exon 2 of the HBB gene, results from a C to T substitution at nucleotide position 118. This changes the amino acid from a glutamine to a stop codon within coding exon 2. This mutation was first reported in the Sardinian population and in an Italian individual with beta0-thalassemia (Trecartin RF et al. J. Clin. Invest., 1981 Oct;68:1012-7; Orkin SH et al. J. Biol. Chem., 1981 Oct;256:9782-4). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. -

alpha Thalassemia

Pathogenic:1

Mar 28, 2019

Centre for Mendelian Genomics, University Medical Centre Ljubljana

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PS1,PM1. -

HBB-related disorder

Pathogenic:1

Dec 24, 2023

PreventionGenetics, part of Exact Sciences

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

The HBB c.118C>T variant is predicted to result in premature protein termination (p.Gln40*). The c.118C>T change is a pathogenic founder variant in Sardina and is also referred to as codon 39C>T (Rosatelli MC et al 1992. PubMed ID: 1734721; Trecartin et al 1981. PubMed ID: 6457059; Sirdah et al. 2013. PubMed ID: 23321370). This variant is reported in 0.062% of alleles in individuals of European (Non-Finnish) descent in gnomAD. This variant is interpreted as pathogenic. -

Heinz body anemia

Pathogenic:1

Apr 10, 2022

DASA

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.118C>T;p.(Gln40*) variant creates a premature translational stop signal in the HBB gene. It is expected to result in an absent or disrupted protein product -PVS1.Well-established in vitro or in vivo functional studies supportive of a damaging effect on the gene or gene product (PMID: 2867271)PS3. This sequence change has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 15402; PMID: 20301599; 27199182; 28361595; 27829304; 28670940; 28366028; 26897028; 32039214; 26366554; 6457059; 28366028) - PS4. The variant is present at low allele frequencies population databases (rs11549407 – gnomAD 0.002695%; ABraOM 0.000854 frequency - https://abraom.ib.usp.br/) - PM2_supporting. The p.(Gln40*) was detected in trans with a pathogenic variant (PMID: 28361595; 26956563) - PM3_strong. In summary, the currently available evidence indicates that the variant is pathogenic. -

Malaria, susceptibility to

Pathogenic:1

Mar 17, 2024

Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: research

- -

Hb SS disease;C0019025:Hereditary persistence of fetal hemoglobin;C0700299:Heinz body anemia;C1840779:METHEMOGLOBINEMIA, BETA TYPE;C1858990:Dominant beta-thalassemia;C1970028:Malaria, susceptibility to;C4693822:Erythrocytosis, familial, 6;CN322236:Beta-thalassemia HBB/LCRB

Pathogenic:1

May 31, 2024

Fulgent Genetics, Fulgent Genetics

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.35

BayesDel_noAF

Pathogenic

0.59

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Pathogenic

1.0

Eigen_PC

Pathogenic

0.84

FATHMM_MKL

Uncertain

0.88

Vest4

0.77

GERP RS

4.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over