Variant 6-31356424-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_005514.8(HLA-B):c.362G>A(p.Ser121Asn) 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. S121R) has been classified as Benign.

Frequency

Genomes: 𝑓 0.00081 ( 0 hom., cov: 4)

Exomes 𝑓: 0.014 ( 94 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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0048499107).

BS2

High AC in GnomAd4 at 36 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-B	NM_005514.8 linkuse as main transcript	c.362G>A	p.Ser121Asn	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>A	p.Ser121Asn	missense_variant	3/8		NM_005514.8	P1

Frequencies

GnomAD3 genomes

AF:

0.000805

AC:

AN:

44696

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000433

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000579

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000671

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00123

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0313

AC:

5711

AN:

182648

Hom.:

447

AF XY:

0.0318

AC XY:

3137

AN XY:

98730

show subpopulations

Gnomad AFR exome

AF:

0.00943

Gnomad AMR exome

AF:

0.0172

Gnomad ASJ exome

AF:

0.0194

Gnomad EAS exome

AF:

0.0319

Gnomad SAS exome

AF:

0.0164

Gnomad FIN exome

AF:

0.0667

Gnomad NFE exome

AF:

0.0360

Gnomad OTH exome

AF:

0.0390

GnomAD4 exome

AF:

0.0139

AC:

11971

AN:

861596

Hom.:

Cov.:

AF XY:

0.0140

AC XY:

6001

AN XY:

427896

show subpopulations

Gnomad4 AFR exome

AF:

0.00432

Gnomad4 AMR exome

AF:

0.0110

Gnomad4 ASJ exome

AF:

0.0140

Gnomad4 EAS exome

AF:

0.00860

Gnomad4 SAS exome

AF:

0.00916

Gnomad4 FIN exome

AF:

0.0208

Gnomad4 NFE exome

AF:

0.0145

Gnomad4 OTH exome

AF:

0.0144

GnomAD4 genome

AF:

0.000805

AC:

AN:

44714

Hom.:

Cov.:

AF XY:

0.000947

AC XY:

AN XY:

21124

show subpopulations

Gnomad4 AFR

AF:

0.000432

Gnomad4 AMR

AF:

0.000578

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000676

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00123

Gnomad4 NFE

AF:

0.00103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0897

Hom.:

ESP6500AA

AF:

0.00110

AC:

ESP6500EA

AF:

0.00620

AC:

ExAC

AF:

0.0356

AC:

4023

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.59

CADD

Benign

4.0

DANN

Benign

0.78

DEOGEN2

Benign

0.018

T;.;T

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.0034

T;T;T

MetaRNN

Benign

0.0048

T;T;T

MetaSVM

Benign

-0.92

MutationTaster

Benign

1.0

PROVEAN

Benign

-0.29

N;.;N

REVEL

Benign

0.063

Sift

Benign

0.19

T;.;T

Sift4G

Benign

0.52

T;.;T

Polyphen

0.0

B;.;.

Vest4

0.045

MPC

0.22

ClinPred

0.0028

GERP RS

-6.4

Varity_R

0.14

gMVP

0.097

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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