Variant rs713031 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005514.8(HLA-B):c.142T>G(p.Ser48Ala) 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 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. S48T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.19 ( 1772 hom., cov: 6)

Exomes 𝑓: 0.17 ( 44219 hom. )

Failed GnomAD Quality Control

Consequence

HLA-B
NM_005514.8 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.74

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 Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0013540089).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-B	NM_005514.8 linkuse as main transcript	c.142T>G	p.Ser48Ala	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.142T>G	p.Ser48Ala	missense_variant	2/8	6	NM_005514.8	ENSP00000399168.2		P01889

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

8907

AN:

46828

Hom.:

1765

Cov.:

FAILED QC

Gnomad AFR

AF:

0.197

Gnomad AMI

AF:

0.198

Gnomad AMR

AF:

0.253

Gnomad ASJ

AF:

0.233

Gnomad EAS

AF:

0.393

Gnomad SAS

AF:

0.389

Gnomad FIN

AF:

0.201

Gnomad MID

AF:

0.442

Gnomad NFE

AF:

0.154

Gnomad OTH

AF:

0.206

GnomAD3 exomes

AF:

0.442

AC:

84226

AN:

190526

Hom.:

24644

AF XY:

0.450

AC XY:

46756

AN XY:

103896

show subpopulations

Gnomad AFR exome

AF:

0.461

Gnomad AMR exome

AF:

0.440

Gnomad ASJ exome

AF:

0.420

Gnomad EAS exome

AF:

0.643

Gnomad SAS exome

AF:

0.571

Gnomad FIN exome

AF:

0.452

Gnomad NFE exome

AF:

0.370

Gnomad OTH exome

AF:

0.417

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.173

AC:

155452

AN:

896142

Hom.:

44219

Cov.:

AF XY:

0.182

AC XY:

81647

AN XY:

447620

show subpopulations

Gnomad4 AFR exome

AF:

0.238

Gnomad4 AMR exome

AF:

0.263

Gnomad4 ASJ exome

AF:

0.284

Gnomad4 EAS exome

AF:

0.536

Gnomad4 SAS exome

AF:

0.404

Gnomad4 FIN exome

AF:

0.238

Gnomad4 NFE exome

AF:

0.131

Gnomad4 OTH exome

AF:

0.202

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.191

AC:

8932

AN:

46882

Hom.:

1772

Cov.:

AF XY:

0.191

AC XY:

4147

AN XY:

21728

show subpopulations

Gnomad4 AFR

AF:

0.197

Gnomad4 AMR

AF:

0.252

Gnomad4 ASJ

AF:

0.233

Gnomad4 EAS

AF:

0.396

Gnomad4 SAS

AF:

0.392

Gnomad4 FIN

AF:

0.201

Gnomad4 NFE

AF:

0.154

Gnomad4 OTH

AF:

0.220

Alfa

AF:

0.266

Hom.:

936

ESP6500AA

AF:

0.461

AC:

1957

ESP6500EA

AF:

0.387

AC:

3187

ExAC

AF:

0.440

AC:

52034

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.56

CADD

Benign

1.6

DANN

Benign

0.17

DEOGEN2

Benign

0.016

T;.;T

Eigen

Benign

-2.3

Eigen_PC

Benign

-2.4

FATHMM_MKL

Benign

0.0056

LIST_S2

Benign

0.0015

T;T;T

MetaRNN

Benign

0.0014

T;T;T

MetaSVM

Benign

-1.0

PROVEAN

Benign

0.55

N;.;N

REVEL

Benign

0.26

Sift

Benign

0.87

T;.;T

Sift4G

Benign

0.83

T;.;T

Polyphen

0.0

B;.;.

Vest4

0.029

MPC

0.18

ClinPred

0.00032

GERP RS

-6.4

Varity_R

0.089

gMVP

0.10

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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