Variant 6-31356719-GT-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_005514.8(HLA-B):c.311del(p.Asn104ThrfsTer47) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.0045 ( 8 hom., cov: 0)

Exomes 𝑓: 0.016 ( 876 hom. )

Failed GnomAD Quality Control

Consequence

HLA-B
NM_005514.8 frameshift

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.82

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP6

Variant 6-31356719-GT-G is Benign according to our data. Variant chr6-31356719-GT-G is described in ClinVar as [Likely_benign]. Clinvar id is 3056094.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-B	NM_005514.8 linkuse as main transcript	c.311del	p.Asn104ThrfsTer47	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.311del	p.Asn104ThrfsTer47	frameshift_variant	2/8		NM_005514.8	P1
	ENST00000603274.1 linkuse as main transcript	n.75del		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

235

AN:

51988

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00136

Gnomad AMI

AF:

0.00962

Gnomad AMR

AF:

0.00231

Gnomad ASJ

AF:

0.00559

Gnomad EAS

AF:

0.0385

Gnomad SAS

AF:

0.0299

Gnomad FIN

AF:

0.00260

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00387

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0182

AC:

3464

AN:

190660

Hom.:

219

AF XY:

0.0189

AC XY:

1929

AN XY:

102262

show subpopulations

Gnomad AFR exome

AF:

0.00799

Gnomad AMR exome

AF:

0.0105

Gnomad ASJ exome

AF:

0.00635

Gnomad EAS exome

AF:

0.0646

Gnomad SAS exome

AF:

0.0253

Gnomad FIN exome

AF:

0.0120

Gnomad NFE exome

AF:

0.0147

Gnomad OTH exome

AF:

0.0202

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0163

AC:

15690

AN:

963112

Hom.:

876

Cov.:

AF XY:

0.0162

AC XY:

7705

AN XY:

474308

show subpopulations

Gnomad4 AFR exome

AF:

0.00574

Gnomad4 AMR exome

AF:

0.00408

Gnomad4 ASJ exome

AF:

0.00553

Gnomad4 EAS exome

AF:

0.0303

Gnomad4 SAS exome

AF:

0.0205

Gnomad4 FIN exome

AF:

0.00233

Gnomad4 NFE exome

AF:

0.0172

Gnomad4 OTH exome

AF:

0.0164

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00452

AC:

235

AN:

52040

Hom.:

Cov.:

AF XY:

0.00492

AC XY:

123

AN XY:

25022

show subpopulations

Gnomad4 AFR

AF:

0.00135

Gnomad4 AMR

AF:

0.00230

Gnomad4 ASJ

AF:

0.00559

Gnomad4 EAS

AF:

0.0386

Gnomad4 SAS

AF:

0.0298

Gnomad4 FIN

AF:

0.00260

Gnomad4 NFE

AF:

0.00387

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

HLA-B-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 17, 2020

This variant is classified as likely 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