Variant chr6-31356732-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_005514.8(HLA-B):c.299A>T(p.Glu100Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.00073 ( 2 hom., cov: 7)

Exomes 𝑓: 0.0079 ( 157 hom. )

Failed GnomAD Quality Control

Consequence

HLA-B
NM_005514.8 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.33

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0026462972).

BS2

High AC in GnomAd4 at 42 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-B	NM_005514.8 link	c.299A>T	p.Glu100Val	missense_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.299A>T	p.Glu100Val	missense_variant	2/8	6	NM_005514.8	ENSP00000399168.2		P01889

Frequencies

GnomAD3 genomes

AF:

0.000732

AC:

AN:

57406

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000786

Gnomad ASJ

AF:

0.000635

Gnomad EAS

AF:

0.00527

Gnomad SAS

AF:

0.00107

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0122

Gnomad NFE

AF:

0.000534

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.0133

AC:

2756

AN:

207848

Hom.:

159

AF XY:

0.0123

AC XY:

1384

AN XY:

112732

show subpopulations

Gnomad AFR exome

AF:

0.00359

Gnomad AMR exome

AF:

0.00914

Gnomad ASJ exome

AF:

0.00399

Gnomad EAS exome

AF:

0.109

Gnomad SAS exome

AF:

0.00776

Gnomad FIN exome

AF:

0.00195

Gnomad NFE exome

AF:

0.00619

Gnomad OTH exome

AF:

0.0120

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00792

AC:

7851

AN:

991846

Hom.:

157

Cov.:

AF XY:

0.00806

AC XY:

3967

AN XY:

492354

show subpopulations

Gnomad4 AFR exome

AF:

0.00926

Gnomad4 AMR exome

AF:

0.00837

Gnomad4 ASJ exome

AF:

0.00454

Gnomad4 EAS exome

AF:

0.0296

Gnomad4 SAS exome

AF:

0.0119

Gnomad4 FIN exome

AF:

0.00257

Gnomad4 NFE exome

AF:

0.00724

Gnomad4 OTH exome

AF:

0.00786

GnomAD4 genome

AF:

0.000731

AC:

AN:

57464

Hom.:

Cov.:

AF XY:

0.000906

AC XY:

AN XY:

27588

show subpopulations

Gnomad4 AFR

AF:

0.000601

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.000635

Gnomad4 EAS

AF:

0.00529

Gnomad4 SAS

AF:

0.00106

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000534

Gnomad4 OTH

AF:

0.00419

Alfa

AF:

0.00763

Hom.:

ExAC

AF:

0.0162

AC:

1946

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

3.5

DANN

Benign

0.48

DEOGEN2

Benign

0.016

T;.;T

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0031

LIST_S2

Benign

0.010

T;T;T

MetaRNN

Benign

0.0026

T;T;T

MetaSVM

Benign

-1.0

PROVEAN

Benign

2.9

N;.;N

REVEL

Uncertain

0.32

Sift

Benign

0.29

T;.;T

Sift4G

Benign

1.0

T;.;T

Polyphen

0.0

B;.;.

Vest4

0.031

MPC

0.26

ClinPred

0.0079

GERP RS

-3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.31

gMVP

0.15

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over