Variant 6-31356716-CA-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP6

The NM_005514.8(HLA-B):c.314delT(p.Leu105fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.0045 ( 8 hom., cov: 6)

Exomes 𝑓: 0.016 ( 799 hom. )

Failed GnomAD Quality Control

Consequence

HLA-B
NM_005514.8 frameshift

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.0870

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:

ENSG00000271581 (HGNC:):

ENSG00000271581 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BP6

Variant 6-31356716-CA-C is Benign according to our data. Variant chr6-31356716-CA-C is described in ClinVar as [Likely_benign]. Clinvar id is 3056409.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-B	NM_005514.8 link	c.314delT	p.Leu105fs	frameshift_variant	2/8	ENST00000412585.7	NP_005505.2	P01889E5FQ95

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-B	ENST00000412585.7 link	c.314delT	p.Leu105fs	frameshift_variant	2/8	6	NM_005514.8	ENSP00000399168.2		P01889

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

247

AN:

54438

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00137

Gnomad AMI

AF:

0.00621

Gnomad AMR

AF:

0.00200

Gnomad ASJ

AF:

0.00620

Gnomad EAS

AF:

0.0354

Gnomad SAS

AF:

0.0251

Gnomad FIN

AF:

0.00299

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00424

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0179

AC:

3497

AN:

195316

Hom.:

229

AF XY:

0.0187

AC XY:

1956

AN XY:

104842

show subpopulations

Gnomad AFR exome

AF:

0.00791

Gnomad AMR exome

AF:

0.00952

Gnomad ASJ exome

AF:

0.00574

Gnomad EAS exome

AF:

0.0661

Gnomad SAS exome

AF:

0.0250

Gnomad FIN exome

AF:

0.0122

Gnomad NFE exome

AF:

0.0143

Gnomad OTH exome

AF:

0.0197

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0161

AC:

15661

AN:

972378

Hom.:

799

Cov.:

AF XY:

0.0160

AC XY:

7666

AN XY:

479090

show subpopulations

Gnomad4 AFR exome

AF:

0.00561

Gnomad4 AMR exome

AF:

0.00368

Gnomad4 ASJ exome

AF:

0.00566

Gnomad4 EAS exome

AF:

0.0301

Gnomad4 SAS exome

AF:

0.0199

Gnomad4 FIN exome

AF:

0.00212

Gnomad4 NFE exome

AF:

0.0171

Gnomad4 OTH exome

AF:

0.0160

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00453

AC:

247

AN:

54494

Hom.:

Cov.:

AF XY:

0.00482

AC XY:

126

AN XY:

26164

show subpopulations

Gnomad4 AFR

AF:

0.00136

Gnomad4 AMR

AF:

0.00200

Gnomad4 ASJ

AF:

0.00620

Gnomad4 EAS

AF:

0.0354

Gnomad4 SAS

AF:

0.0250

Gnomad4 FIN

AF:

0.00299

Gnomad4 NFE

AF:

0.00424

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

HLA-B-related disorder

Benign:1

Likely benign, no assertion criteria provided

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