Variant 6-31356889-A-T 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>A(p.Ser48Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/18 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. S48A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.040 ( 107 hom., cov: 6)

Exomes 𝑓: 0.085 ( 14356 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=0.003454417).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-B	NM_005514.8 linkuse as main transcript	c.142T>A	p.Ser48Thr	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>A	p.Ser48Thr	missense_variant	2/8	6	NM_005514.8	ENSP00000399168.2		P01889

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

1874

AN:

47074

Hom.:

109

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0167

Gnomad AMI

AF:

0.0430

Gnomad AMR

AF:

0.0259

Gnomad ASJ

AF:

0.0259

Gnomad EAS

AF:

0.135

Gnomad SAS

AF:

0.0372

Gnomad FIN

AF:

0.0375

Gnomad MID

AF:

0.0682

Gnomad NFE

AF:

0.0510

Gnomad OTH

AF:

0.0504

GnomAD3 exomes

AF:

0.144

AC:

27432

AN:

190526

Hom.:

5004

AF XY:

0.146

AC XY:

15147

AN XY:

103896

show subpopulations

Gnomad AFR exome

AF:

0.0635

Gnomad AMR exome

AF:

0.147

Gnomad ASJ exome

AF:

0.0823

Gnomad EAS exome

AF:

0.204

Gnomad SAS exome

AF:

0.178

Gnomad FIN exome

AF:

0.160

Gnomad NFE exome

AF:

0.135

Gnomad OTH exome

AF:

0.172

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0849

AC:

74048

AN:

872498

Hom.:

14356

Cov.:

AF XY:

0.0877

AC XY:

38303

AN XY:

436780

show subpopulations

Gnomad4 AFR exome

AF:

0.0507

Gnomad4 AMR exome

AF:

0.0781

Gnomad4 ASJ exome

AF:

0.0516

Gnomad4 EAS exome

AF:

0.152

Gnomad4 SAS exome

AF:

0.125

Gnomad4 FIN exome

AF:

0.0896

Gnomad4 NFE exome

AF:

0.0811

Gnomad4 OTH exome

AF:

0.0879

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0397

AC:

1872

AN:

47122

Hom.:

107

Cov.:

AF XY:

0.0366

AC XY:

804

AN XY:

21996

show subpopulations

Gnomad4 AFR

AF:

0.0168

Gnomad4 AMR

AF:

0.0259

Gnomad4 ASJ

AF:

0.0259

Gnomad4 EAS

AF:

0.133

Gnomad4 SAS

AF:

0.0346

Gnomad4 FIN

AF:

0.0375

Gnomad4 NFE

AF:

0.0510

Gnomad4 OTH

AF:

0.0509

Alfa

AF:

0.184

Hom.:

936

ExAC

AF:

0.142

AC:

16797

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.53

CADD

Benign

1.6

DANN

Benign

0.27

DEOGEN2

Benign

0.022

T;.;T

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.3

FATHMM_MKL

Benign

0.0073

LIST_S2

Benign

0.0027

T;T;T

MetaRNN

Benign

0.0035

T;T;T

MetaSVM

Benign

-1.0

PROVEAN

Benign

-0.78

N;.;N

REVEL

Uncertain

0.32

Sift

Benign

0.33

T;.;T

Sift4G

Benign

0.15

T;.;T

Polyphen

0.0

B;.;.

Vest4

0.046

MPC

0.20

ClinPred

0.0024

GERP RS

-6.4

Varity_R

0.13

gMVP

0.18

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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