Variant rs2308466 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005514.8(HLA-B):c.560A>T(p.Glu187Val) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E187L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.11 ( 460 hom., cov: 4)

Exomes 𝑓: 0.23 ( 16763 hom. )

Failed GnomAD Quality Control

Consequence

HLA-B
NM_005514.8 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -8.96

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0052467883).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-B	NM_005514.8 linkuse as main transcript	c.560A>T	p.Glu187Val	missense_variant	3/8	ENST00000412585.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-B	ENST00000412585.7 linkuse as main transcript	c.560A>T	p.Glu187Val	missense_variant	3/8		NM_005514.8	P1

Frequencies

GnomAD3 genomes

AF:

0.111

AC:

3500

AN:

31468

Hom.:

460

Cov.:

show subpopulations

Gnomad AFR

AF:

0.176

Gnomad AMI

AF:

0.152

Gnomad AMR

AF:

0.166

Gnomad ASJ

AF:

0.139

Gnomad EAS

AF:

0.151

Gnomad SAS

AF:

0.183

Gnomad FIN

AF:

0.0436

Gnomad MID

AF:

0.459

Gnomad NFE

AF:

0.0778

Gnomad OTH

AF:

0.219

GnomAD3 exomes

AF:

0.381

AC:

64927

AN:

170240

Hom.:

6716

AF XY:

0.381

AC XY:

35450

AN XY:

92970

show subpopulations

Gnomad AFR exome

AF:

0.432

Gnomad AMR exome

AF:

0.435

Gnomad ASJ exome

AF:

0.321

Gnomad EAS exome

AF:

0.480

Gnomad SAS exome

AF:

0.404

Gnomad FIN exome

AF:

0.342

Gnomad NFE exome

AF:

0.348

Gnomad OTH exome

AF:

0.384

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.231

AC:

209131

AN:

905958

Hom.:

16763

Cov.:

AF XY:

0.232

AC XY:

106037

AN XY:

456104

show subpopulations

Gnomad4 AFR exome

AF:

0.392

Gnomad4 AMR exome

AF:

0.329

Gnomad4 ASJ exome

AF:

0.323

Gnomad4 EAS exome

AF:

0.300

Gnomad4 SAS exome

AF:

0.297

Gnomad4 FIN exome

AF:

0.169

Gnomad4 NFE exome

AF:

0.211

Gnomad4 OTH exome

AF:

0.257

GnomAD4 genome

AF:

0.111

AC:

3501

AN:

31466

Hom.:

460

Cov.:

AF XY:

0.108

AC XY:

1594

AN XY:

14806

show subpopulations

Gnomad4 AFR

AF:

0.177

Gnomad4 AMR

AF:

0.168

Gnomad4 ASJ

AF:

0.139

Gnomad4 EAS

AF:

0.152

Gnomad4 SAS

AF:

0.179

Gnomad4 FIN

AF:

0.0436

Gnomad4 NFE

AF:

0.0777

Gnomad4 OTH

AF:

0.216

Alfa

AF:

0.307

Hom.:

515

ESP6500AA

AF:

0.542

AC:

2317

ESP6500EA

AF:

0.464

AC:

3870

ExAC

AF:

0.381

AC:

45558

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.49

CADD

Benign

0.076

DANN

Benign

0.47

DEOGEN2

Benign

0.026

T;.;T

Eigen

Benign

-2.3

Eigen_PC

Benign

-2.5

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.0019

T;T;T

MetaRNN

Benign

0.0052

T;T;T

MetaSVM

Benign

-0.92

MutationTaster

Benign

1.0

PROVEAN

Benign

-1.9

N;.;N

REVEL

Benign

0.24

Sift

Benign

0.055

T;.;T

Sift4G

Benign

0.19

T;.;T

Polyphen

0.019

B;.;.

Vest4

0.042

MPC

0.27

ClinPred

0.028

GERP RS

-6.4

Varity_R

0.57

gMVP

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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