6-31356754-C-T

Position:

chr6-31356754-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_005514.8(HLA-B):c.277G>A(p.Ala93Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A93R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.43 ( 5437 hom., cov: 5)

Exomes 𝑓: 0.66 ( 264581 hom. )

Failed GnomAD Quality Control

Consequence

HLA-B
NM_005514.8 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -3.32

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.3709429E-6).

BP6

Variant 6-31356754-C-T is Benign according to our data. Variant chr6-31356754-C-T is described in ClinVar as [Benign]. Clinvar id is 3061033.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-B	NM_005514.8 linkuse as main transcript	c.277G>A	p.Ala93Thr	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 linkuse as main transcript	c.277G>A	p.Ala93Thr	missense_variant	2/8	6	NM_005514.8	ENSP00000399168.2		P01889

Frequencies

GnomAD3 genomes

AF:

0.432

AC:

15957

AN:

36896

Hom.:

5432

Cov.:

show subpopulations

Gnomad AFR

AF:

0.284

Gnomad AMI

AF:

0.636

Gnomad AMR

AF:

0.597

Gnomad ASJ

AF:

0.825

Gnomad EAS

AF:

0.521

Gnomad SAS

AF:

0.466

Gnomad FIN

AF:

0.426

Gnomad MID

AF:

0.733

Gnomad NFE

AF:

0.438

Gnomad OTH

AF:

0.471

GnomAD3 exomes

AF:

0.766

AC:

149551

AN:

195270

Hom.:

64720

AF XY:

0.768

AC XY:

82003

AN XY:

106720

show subpopulations

Gnomad AFR exome

AF:

0.655

Gnomad AMR exome

AF:

0.898

Gnomad ASJ exome

AF:

0.874

Gnomad EAS exome

AF:

0.720

Gnomad SAS exome

AF:

0.819

Gnomad FIN exome

AF:

0.738

Gnomad NFE exome

AF:

0.720

Gnomad OTH exome

AF:

0.766

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.662

AC:

600088

AN:

907044

Hom.:

264581

Cov.:

AF XY:

0.666

AC XY:

300379

AN XY:

450786

show subpopulations

Gnomad4 AFR exome

AF:

0.512

Gnomad4 AMR exome

AF:

0.858

Gnomad4 ASJ exome

AF:

0.873

Gnomad4 EAS exome

AF:

0.635

Gnomad4 SAS exome

AF:

0.785

Gnomad4 FIN exome

AF:

0.588

Gnomad4 NFE exome

AF:

0.645

Gnomad4 OTH exome

AF:

0.679

GnomAD4 genome

AF:

0.433

AC:

15979

AN:

36942

Hom.:

5437

Cov.:

AF XY:

0.426

AC XY:

7462

AN XY:

17512

show subpopulations

Gnomad4 AFR

AF:

0.285

Gnomad4 AMR

AF:

0.598

Gnomad4 ASJ

AF:

0.825

Gnomad4 EAS

AF:

0.521

Gnomad4 SAS

AF:

0.470

Gnomad4 FIN

AF:

0.426

Gnomad4 NFE

AF:

0.438

Gnomad4 OTH

AF:

0.467

Alfa

AF:

0.641

Hom.:

3628

ESP6500AA

AF:

0.632

AC:

2616

ESP6500EA

AF:

0.656

AC:

5337

ExAC

AF:

0.694

AC:

82387

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

HLA-B-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 17, 2020

This variant is classified as 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

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.54

CADD

Benign

5.0

DANN

Benign

0.84

DEOGEN2

Benign

0.020

T;.;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0068

LIST_S2

Benign

0.045

T;T;T

MetaRNN

Benign

0.0000024

T;T;T

MetaSVM

Benign

-1.0

PROVEAN

Benign

-0.44

N;.;N

REVEL

Benign

0.29

Sift

Benign

0.52

T;.;T

Sift4G

Benign

0.37

T;.;T

Polyphen

0.0

B;.;.

Vest4

0.047

MPC

0.22

ClinPred

0.00033

GERP RS

-2.7

Varity_R

0.066

gMVP

0.047

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