dbSNP rs1065378: HLA-B:p.Arg59Trp (chr6-31356856-T-A) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_005514.8(HLA-B):c.175A>T(p.Arg59Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 9)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HLA-B
NM_005514.8 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.221

Publications

0 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.33180374).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-B	NM_005514.8 link	c.175A>T	p.Arg59Trp	missense_variant	Exon 2 of 8	ENST00000412585.7	NP_005505.2	P01889E5FQ95

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-B	ENST00000412585.7 link	c.175A>T	p.Arg59Trp	missense_variant	Exon 2 of 8	6	NM_005514.8	ENSP00000399168.2		P01889

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

67996

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1089908

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

542270

African (AFR)

AF:

0.00

AC:

AN:

23304

American (AMR)

AF:

0.00

AC:

AN:

33342

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21402

East Asian (EAS)

AF:

0.00

AC:

AN:

26588

South Asian (SAS)

AF:

0.00

AC:

AN:

58780

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35856

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3096

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

842474

Other (OTH)

AF:

0.00

AC:

AN:

45066

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

68074

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

32206

African (AFR)

AF:

0.00

AC:

AN:

17216

American (AMR)

AF:

0.00

AC:

AN:

6390

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2054

East Asian (EAS)

AF:

0.00

AC:

AN:

1558

South Asian (SAS)

AF:

0.00

AC:

AN:

1286

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4702

Middle Eastern (MID)

AF:

0.00

AC:

AN:

140

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

33524

Other (OTH)

AF:

0.00

AC:

AN:

816

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.032

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.048

T;.;T

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.42

T;T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.33

T;T;T

MetaSVM

Benign

-0.98

PhyloP100

-0.22

PROVEAN

Pathogenic

-6.4

D;.;D

REVEL

Benign

0.16

Sift

Uncertain

0.012

D;.;D

Sift4G

Uncertain

0.012

D;.;D

Polyphen

0.0080

B;.;.

Vest4

0.29

MutPred

0.63

Loss of disorder (P = 0.0028);Loss of disorder (P = 0.0028);.;

MVP

0.23

MPC

0.23

ClinPred

0.42

GERP RS

1.2

PromoterAI

0.084

Neutral

(source)

Varity_R

0.28

gMVP

0.29

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.20

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.20

Position offset: -11

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over