Variant rs1071652 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_005514.8(HLA-B):c.362G>T(p.Ser121Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts 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. S121R) has been classified as Benign.

Frequency

Genomes: 𝑓 0.00042 ( 0 hom., cov: 4)

Exomes 𝑓: 0.0032 ( 26 hom. )

Consequence

HLA-B
NM_005514.8 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.73

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAd4 at 19 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-B	NM_005514.8 linkuse as main transcript	c.362G>T	p.Ser121Ile	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.362G>T	p.Ser121Ile	missense_variant	3/8		NM_005514.8	P1

Frequencies

GnomAD3 genomes

AF:

0.000425

AC:

AN:

44734

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.00495

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:

0.000215

Gnomad OTH

AF:

0.00219

GnomAD3 exomes

AF:

0.0198

AC:

3623

AN:

182648

Hom.:

260

AF XY:

0.0203

AC XY:

2007

AN XY:

98730

show subpopulations

Gnomad AFR exome

AF:

0.0446

Gnomad AMR exome

AF:

0.0110

Gnomad ASJ exome

AF:

0.0363

Gnomad EAS exome

AF:

0.00165

Gnomad SAS exome

AF:

0.0396

Gnomad FIN exome

AF:

0.00643

Gnomad NFE exome

AF:

0.0189

Gnomad OTH exome

AF:

0.0233

GnomAD4 exome

AF:

0.00320

AC:

2789

AN:

871158

Hom.:

Cov.:

AF XY:

0.00352

AC XY:

1522

AN XY:

432650

show subpopulations

Gnomad4 AFR exome

AF:

0.00571

Gnomad4 AMR exome

AF:

0.00347

Gnomad4 ASJ exome

AF:

0.00936

Gnomad4 EAS exome

AF:

0.000428

Gnomad4 SAS exome

AF:

0.00952

Gnomad4 FIN exome

AF:

0.000824

Gnomad4 NFE exome

AF:

0.00269

Gnomad4 OTH exome

AF:

0.00438

GnomAD4 genome

AF:

0.000425

AC:

AN:

44752

Hom.:

Cov.:

AF XY:

0.000426

AC XY:

AN XY:

21134

show subpopulations

Gnomad4 AFR

AF:

0.00104

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000215

Gnomad4 OTH

AF:

0.00216

Alfa

AF:

0.0150

Hom.:

ExAC

AF:

0.0288

AC:

3246

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.022

T;.;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.048

LIST_S2

Benign

0.0037

T;T;T

MetaRNN

Benign

0.0053

T;T;T

MetaSVM

Benign

-0.87

MutationTaster

Benign

1.0

PROVEAN

Benign

-1.2

N;.;N

REVEL

Benign

0.24

Sift

Benign

0.17

T;.;D

Sift4G

Benign

0.26

T;.;T

Polyphen

0.78

P;.;.

Vest4

0.049

MPC

0.73

ClinPred

0.021

GERP RS

-6.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.23

gMVP

0.18

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.32

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.32

Position offset: 1

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