Variant 6-31356711-C-CGG 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.319_320insCC(p.Gly107fs) 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 0.0038 ( 8 hom., cov: 3)

Exomes 𝑓: 0.015 ( 948 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: -1.91

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BP6

Variant 6-31356711-C-CGG is Benign according to our data. Variant chr6-31356711-C-CGG is described in ClinVar as [Likely_benign]. Clinvar id is 3055858.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.319_320insCC	p.Gly107fs	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.319_320insCC	p.Gly107fs	frameshift_variant	2/8	6	NM_005514.8	ENSP00000399168.2		P01889

Frequencies

GnomAD3 genomes

AF:

0.00376

AC:

241

AN:

64114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00107

Gnomad AMI

AF:

0.00266

Gnomad AMR

AF:

0.00186

Gnomad ASJ

AF:

0.00286

Gnomad EAS

AF:

0.0279

Gnomad SAS

AF:

0.0208

Gnomad FIN

AF:

0.00236

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00373

Gnomad OTH

AF:

0.00125

GnomAD3 exomes

AF:

0.0201

AC:

4017

AN:

199372

Hom.:

315

AF XY:

0.0211

AC XY:

2259

AN XY:

107050

show subpopulations

Gnomad AFR exome

AF:

0.00781

Gnomad AMR exome

AF:

0.0103

Gnomad ASJ exome

AF:

0.00670

Gnomad EAS exome

AF:

0.0646

Gnomad SAS exome

AF:

0.0246

Gnomad FIN exome

AF:

0.0150

Gnomad NFE exome

AF:

0.0188

Gnomad OTH exome

AF:

0.0190

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0146

AC:

16140

AN:

1106300

Hom.:

948

Cov.:

AF XY:

0.0144

AC XY:

7890

AN XY:

548440

show subpopulations

Gnomad4 AFR exome

AF:

0.00447

Gnomad4 AMR exome

AF:

0.00326

Gnomad4 ASJ exome

AF:

0.00324

Gnomad4 EAS exome

AF:

0.0249

Gnomad4 SAS exome

AF:

0.0145

Gnomad4 FIN exome

AF:

0.00205

Gnomad4 NFE exome

AF:

0.0159

Gnomad4 OTH exome

AF:

0.0145

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00376

AC:

241

AN:

64180

Hom.:

Cov.:

AF XY:

0.00384

AC XY:

119

AN XY:

30972

show subpopulations

Gnomad4 AFR

AF:

0.00107

Gnomad4 AMR

AF:

0.00186

Gnomad4 ASJ

AF:

0.00286

Gnomad4 EAS

AF:

0.0280

Gnomad4 SAS

AF:

0.0207

Gnomad4 FIN

AF:

0.00236

Gnomad4 NFE

AF:

0.00373

Gnomad4 OTH

AF:

0.00122

Alfa

AF:

0.0728

Hom.:

407

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

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