dbSNP rs7946748: HBB:c.*60C>T (chr11-5226496-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000485743(HBB):c.*60C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 1,277,896 control chromosomes in the GnomAD database, including 9,166 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 936 hom., cov: 32)

Exomes 𝑓: 0.12 ( 8230 hom. )

Consequence

HBB
ENST00000485743 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.445

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 11-5226496-G-A is Benign according to our data. Variant chr11-5226496-G-A is described in ClinVar as [Benign]. Clinvar id is 439774.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-5226496-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HBB	NM_000518.5 link	c.315+81C>T		intron_variant	Intron 2 of 2	ENST00000335295.4	NP_000509.1	P68871D9YZU5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HBB	ENST00000335295.4 link	c.315+81C>T		intron_variant	Intron 2 of 2	1	NM_000518.5	ENSP00000333994.3		P68871

Frequencies

GnomAD3 genomes

AF:

0.106

AC:

16061

AN:

152074

Hom.:

933

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0789

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.0916

Gnomad ASJ

AF:

0.0879

Gnomad EAS

AF:

0.0212

Gnomad SAS

AF:

0.171

Gnomad FIN

AF:

0.152

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.122

Gnomad OTH

AF:

0.104

GnomAD4 exome

AF:

0.116

AC:

130932

AN:

1125704

Hom.:

8230

Cov.:

AF XY:

0.119

AC XY:

68619

AN XY:

574284

show subpopulations

Gnomad4 AFR exome

AF:

0.0739

Gnomad4 AMR exome

AF:

0.0668

Gnomad4 ASJ exome

AF:

0.0929

Gnomad4 EAS exome

AF:

0.0163

Gnomad4 SAS exome

AF:

0.174

Gnomad4 FIN exome

AF:

0.145

Gnomad4 NFE exome

AF:

0.119

Gnomad4 OTH exome

AF:

0.111

GnomAD4 genome

AF:

0.106

AC:

16062

AN:

152192

Hom.:

936

Cov.:

AF XY:

0.107

AC XY:

7997

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.0788

Gnomad4 AMR

AF:

0.0914

Gnomad4 ASJ

AF:

0.0879

Gnomad4 EAS

AF:

0.0214

Gnomad4 SAS

AF:

0.170

Gnomad4 FIN

AF:

0.152

Gnomad4 NFE

AF:

0.122

Gnomad4 OTH

AF:

0.105

Alfa

AF:

0.118

Hom.:

1083

Bravo

AF:

0.0944

Asia WGS

AF:

0.100

AC:

347

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

beta Thalassemia

Benign:4

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

- -

Jan 01, 2018

College of Science, Al Muthanna University, Al Muthanna University

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: research

- -

Jul 01, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:4

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 16, 2020

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.83

DANN

Benign

0.70

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