chr11-5227411-G-A

Variant names:

• chr11-5227411-G-A
• rs10742583
• ENST00000380315.2:c.-19+101C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000380315.2(HBB):​c.-19+101C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.795 in 279,618 control chromosomes in the GnomAD database, including 89,883 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.82 (51722 hom., cov: 31)
  • Exomes 𝑓: 0.77 (38161 hom.)
• Consequence: HBB ENST00000380315.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.0930
• Publications: 11 publications found

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 Gene-Disease associations (from GenCC):

• dominant beta-thalassemia

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), ClinGen
• hemoglobin M disease

  Inheritance: AD Classification: DEFINITIVE, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, ClinGen
• beta thalassemia

  Inheritance: AR Classification: DEFINITIVE Submitted by: Myriad Women’s Health
• beta-thalassemia HBB/LCRB

  Inheritance: AR, SD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
• sickle cell disease and related diseases

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• erythrocytosis, familial, 6

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• Heinz body anemia

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• sickle cell disease

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
• hereditary persistence of fetal hemoglobin-beta-thalassemia syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• beta-thalassemia intermedia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• beta-thalassemia major

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• delta-beta-thalassemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• hemoglobin C disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• hemoglobin C-beta-thalassemia syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• hemoglobin E disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• hemoglobin E-beta-thalassemia syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• hereditary persistence of fetal hemoglobin-sickle cell disease syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• sickle cell-beta-thalassemia disease syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• sickle cell-hemoglobin c disease syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• sickle cell-hemoglobin d disease syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• sickle cell-hemoglobin E disease syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000298932 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 11-5227411-G-A is Benign according to our data. Variant chr11-5227411-G-A is described in ClinVar as Benign. ClinVar VariationId is 869329.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.873 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000380315.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HBB	ENST00000380315.2	TSL:5	c.-19+101C>T		intron	N/A	ENSP00000369671.2
	ENSG00000298932	ENST00000759072.1		n.265+1683G>A		intron	N/A
	HBB	ENST00000647020.1		c.-390C>T		upstream_gene	N/A	ENSP00000494175.1

Frequencies

GnomAD3 genomes AF: 0.820 AC: 124630 AN: 152036 Hom.: 51690 Cov.: 31

Gnomad AFR AF: 0.881

Gnomad AMI AF: 0.971

Gnomad AMR AF: 0.735

Gnomad ASJ AF: 0.869

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.636

Gnomad FIN AF: 0.783

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.841

Gnomad OTH AF: 0.828

GnomAD4 exome AF: 0.766 AC: 97584 AN: 127464 Hom.: 38161 AF XY: 0.748 AC XY: 50260 AN XY: 67156

African (AFR) AF: 0.879 AC: 3795 AN: 4316

American (AMR) AF: 0.689 AC: 4053 AN: 5882

Ashkenazi Jewish (ASJ) AF: 0.858 AC: 2733 AN: 3186

East Asian (EAS) AF: 0.475 AC: 3158 AN: 6644

South Asian (SAS) AF: 0.611 AC: 12884 AN: 21086

European-Finnish (FIN) AF: 0.772 AC: 4240 AN: 5494

Middle Eastern (MID) AF: 0.882 AC: 413 AN: 468

European-Non Finnish (NFE) AF: 0.827 AC: 61022 AN: 73748

Other (OTH) AF: 0.796 AC: 5286 AN: 6640

GnomAD4 genome AF: 0.820 AC: 124719 AN: 152154 Hom.: 51722 Cov.: 31 AF XY: 0.811 AC XY: 60328 AN XY: 74380

African (AFR) AF: 0.880 AC: 36543 AN: 41510

American (AMR) AF: 0.734 AC: 11221 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.869 AC: 3014 AN: 3470

East Asian (EAS) AF: 0.489 AC: 2525 AN: 5162

South Asian (SAS) AF: 0.637 AC: 3065 AN: 4814

European-Finnish (FIN) AF: 0.783 AC: 8294 AN: 10588

Middle Eastern (MID) AF: 0.850 AC: 250 AN: 294

European-Non Finnish (NFE) AF: 0.841 AC: 57179 AN: 68012

Other (OTH) AF: 0.824 AC: 1744 AN: 2116

Alfa AF: 0.824 Hom.: 63232

Bravo AF: 0.824

Asia WGS AF: 0.580 AC: 2020 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

beta Thalassemia Benign:1

Nov 25, 2019

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

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: curation

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.20
DANN	Benign	0.50
PhyloP100		-0.093
PromoterAI		-0.0024	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs10742583; hg19: chr11-5248641;