Variant 6-31356747-GCC-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_005514.8(HLA-B):c.282_283del(p.Gln94HisfsTer4) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.621 in 968,846 control chromosomes in the GnomAD database, including 261,513 homozygotes. Variant has been reported in ClinVar as Benign (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.34 ( 5022 hom., cov: 0)

Exomes 𝑓: 0.63 ( 256491 hom. )

Consequence

HLA-B
NM_005514.8 frameshift

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.06

Variant links:

Genes affected

HLA-B (HGNC:4932): (major histocompatibility complex, class I, B) HLA-B belongs to the HLA class I heavy chain paralogues. This class I molecule is a heterodimer consisting of a heavy chain and a light chain (beta-2 microglobulin). The heavy chain is anchored in the membrane. Class I molecules play a central role in the immune system by presenting peptides derived from the endoplasmic reticulum lumen. They are expressed in nearly all cells. The heavy chain is approximately 45 kDa and its gene contains 8 exons. Exon 1 encodes the leader peptide, exon 2 and 3 encode the alpha1 and alpha2 domains, which both bind the peptide, exon 4 encodes the alpha3 domain, exon 5 encodes the transmembrane region and exons 6 and 7 encode the cytoplasmic tail. Polymorphisms within exon 2 and exon 3 are responsible for the peptide binding specificity of each class one molecule. Typing for these polymorphisms is routinely done for bone marrow and kidney transplantation. Hundreds of HLA-B alleles have been described. [provided by RefSeq, Jul 2008]

HLA-B links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 6-31356747-GCC-G is Benign according to our data. Variant chr6-31356747-GCC-G is described in ClinVar as [Benign]. Clinvar id is 3060355.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-B	NM_005514.8 linkuse as main transcript	c.282_283del	p.Gln94HisfsTer4	frameshift_variant	2/8	ENST00000412585.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-B	ENST00000412585.7 linkuse as main transcript	c.282_283del	p.Gln94HisfsTer4	frameshift_variant	2/8		NM_005514.8	P1
	ENST00000603274.1 linkuse as main transcript	n.102_103del		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.341

AC:

15063

AN:

44178

Hom.:

5020

Cov.:

show subpopulations

Gnomad AFR

AF:

0.207

Gnomad AMI

AF:

0.567

Gnomad AMR

AF:

0.486

Gnomad ASJ

AF:

0.769

Gnomad EAS

AF:

0.404

Gnomad SAS

AF:

0.349

Gnomad FIN

AF:

0.336

Gnomad MID

AF:

0.532

Gnomad NFE

AF:

0.356

Gnomad OTH

AF:

0.360

GnomAD3 exomes

AF:

0.729

AC:

147448

AN:

202136

Hom.:

61708

AF XY:

0.733

AC XY:

80711

AN XY:

110080

show subpopulations

Gnomad AFR exome

AF:

0.622

Gnomad AMR exome

AF:

0.865

Gnomad ASJ exome

AF:

0.852

Gnomad EAS exome

AF:

0.642

Gnomad SAS exome

AF:

0.789

Gnomad FIN exome

AF:

0.716

Gnomad NFE exome

AF:

0.685

Gnomad OTH exome

AF:

0.726

GnomAD4 exome

AF:

0.634

AC:

586316

AN:

924616

Hom.:

256491

AF XY:

0.639

AC XY:

293311

AN XY:

459196

show subpopulations

Gnomad4 AFR exome

AF:

0.479

Gnomad4 AMR exome

AF:

0.829

Gnomad4 ASJ exome

AF:

0.845

Gnomad4 EAS exome

AF:

0.581

Gnomad4 SAS exome

AF:

0.760

Gnomad4 FIN exome

AF:

0.562

Gnomad4 NFE exome

AF:

0.618

Gnomad4 OTH exome

AF:

0.650

GnomAD4 genome

AF:

0.341

AC:

15076

AN:

44230

Hom.:

5022

Cov.:

AF XY:

0.335

AC XY:

7050

AN XY:

21066

show subpopulations

Gnomad4 AFR

AF:

0.207

Gnomad4 AMR

AF:

0.488

Gnomad4 ASJ

AF:

0.769

Gnomad4 EAS

AF:

0.403

Gnomad4 SAS

AF:

0.351

Gnomad4 FIN

AF:

0.336

Gnomad4 NFE

AF:

0.356

Gnomad4 OTH

AF:

0.353

Alfa

AF:

0.388

Hom.:

4017

Asia WGS

AF:

0.757

AC:

2634

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

HLA-B-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 17, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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