dbSNP rs1050683: HLA-B:p.Ala182Thr (chr6-31356242-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

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

The NM_005514.8(HLA-B):c.544G>A(p.Ala182Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/19 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 0.00046 ( 0 hom., cov: 6)

Exomes 𝑓: 0.0038 ( 62 hom. )

Failed GnomAD Quality Control

Consequence

HLA-B
NM_005514.8 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.587

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0057958066).

BS2

High AC in GnomAd4 at 24 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-B	NM_005514.8 link	c.544G>A	p.Ala182Thr	missense_variant	Exon 3 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.544G>A	p.Ala182Thr	missense_variant	Exon 3 of 8	6	NM_005514.8	ENSP00000399168.2		P01889

Frequencies

GnomAD3 genomes

AF:

0.000462

AC:

AN:

51966

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000355

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000707

Gnomad ASJ

AF:

0.00175

Gnomad EAS

AF:

0.000488

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000540

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00595

AC:

1397

AN:

234822

Hom.:

AF XY:

0.00513

AC XY:

658

AN XY:

128330

show subpopulations

Gnomad AFR exome

AF:

0.00189

Gnomad AMR exome

AF:

0.0224

Gnomad ASJ exome

AF:

0.00990

Gnomad EAS exome

AF:

0.0143

Gnomad SAS exome

AF:

0.00211

Gnomad FIN exome

AF:

0.000479

Gnomad NFE exome

AF:

0.00206

Gnomad OTH exome

AF:

0.00825

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00376

AC:

4612

AN:

1227090

Hom.:

Cov.:

AF XY:

0.00388

AC XY:

2368

AN XY:

610758

show subpopulations

Gnomad4 AFR exome

AF:

0.00203

Gnomad4 AMR exome

AF:

0.0145

Gnomad4 ASJ exome

AF:

0.0207

Gnomad4 EAS exome

AF:

0.0135

Gnomad4 SAS exome

AF:

0.00449

Gnomad4 FIN exome

AF:

0.00639

Gnomad4 NFE exome

AF:

0.00249

Gnomad4 OTH exome

AF:

0.00547

GnomAD4 genome

AF:

0.000462

AC:

AN:

51972

Hom.:

Cov.:

AF XY:

0.000406

AC XY:

AN XY:

24642

show subpopulations

Gnomad4 AFR

AF:

0.000354

Gnomad4 AMR

AF:

0.000706

Gnomad4 ASJ

AF:

0.00175

Gnomad4 EAS

AF:

0.000489

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000540

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00948

Hom.:

ExAC

AF:

0.00337

AC:

405

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.024

T;.;T

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.045

LIST_S2

Benign

0.088

T;T;T

M_CAP

Benign

0.0029

MetaRNN

Benign

0.0058

T;T;T

MetaSVM

Benign

-0.93

PROVEAN

Benign

-1.1

N;.;N

REVEL

Benign

0.13

Sift

Benign

0.25

T;.;T

Sift4G

Benign

0.13

T;.;T

Polyphen

0.0050

B;.;.

Vest4

0.16

MVP

0.067

MPC

0.22

ClinPred

0.021

GERP RS

-0.21

Varity_R

0.21

gMVP

0.078

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