Variant 6-31355138-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_005514.8(HLA-B):c.981C>T(p.Val327Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00010 ( 0 hom., cov: 9)

Exomes 𝑓: 0.000034 ( 1 hom. )

Consequence

HLA-B
NM_005514.8 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.75

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:

HLA-B (HGNC:):

HLA-B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 6-31355138-G-A is Benign according to our data. Variant chr6-31355138-G-A is described in ClinVar as [Benign]. Clinvar id is 752503.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-3.75 with no splicing effect.

BS2

High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-B	NM_005514.8 linkuse as main transcript	c.981C>T	p.Val327Val	synonymous_variant	5/8	ENST00000412585.7	NP_005505.2	P01889E5FQ95

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-B	ENST00000412585.7 linkuse as main transcript	c.981C>T	p.Val327Val	synonymous_variant	5/8	6	NM_005514.8	ENSP00000399168.2		P01889

Frequencies

GnomAD3 genomes

AF:

0.000100

AC:

AN:

69898

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000426

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000257

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000270

AC:

AN:

248126

Hom.:

AF XY:

0.000156

AC XY:

AN XY:

134298

show subpopulations

Gnomad AFR exome

AF:

0.00353

Gnomad AMR exome

AF:

0.000263

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000331

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000892

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000342

AC:

AN:

1052250

Hom.:

Cov.:

AF XY:

0.0000383

AC XY:

AN XY:

521550

show subpopulations

Gnomad4 AFR exome

AF:

0.000882

Gnomad4 AMR exome

AF:

0.0000996

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000474

Gnomad4 SAS exome

AF:

0.0000433

Gnomad4 FIN exome

AF:

0.0000286

Gnomad4 NFE exome

AF:

0.0000143

Gnomad4 OTH exome

AF:

0.0000238

GnomAD4 genome

AF:

0.000100

AC:

AN:

69908

Hom.:

Cov.:

AF XY:

0.0000911

AC XY:

AN XY:

32916

show subpopulations

Gnomad4 AFR

AF:

0.000425

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000257

Gnomad4 OTH

AF:

0.00

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 18, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

5.3

DANN

Benign

0.51

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