Variant 6-31356418-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4BA1

The NM_005514.8(HLA-B):c.368A>G(p.Tyr123Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/19 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. Y123F) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0019 ( 0 hom., cov: 5)

Exomes 𝑓: 0.018 ( 385 hom. )

Failed GnomAD Quality Control

Consequence

HLA-B
NM_005514.8 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.869

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.420279).

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-B	NM_005514.8 link	c.368A>G	p.Tyr123Cys	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.368A>G	p.Tyr123Cys	missense_variant	Exon 3 of 8	6	NM_005514.8	ENSP00000399168.2		P01889

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

46284

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000170

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00142

Gnomad ASJ

AF:

0.00685

Gnomad EAS

AF:

0.0120

Gnomad SAS

AF:

0.00617

Gnomad FIN

AF:

0.00243

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00200

Gnomad OTH

AF:

0.00212

GnomAD3 exomes

AF:

0.00000996

AC:

AN:

200890

Hom.:

AF XY:

0.00000913

AC XY:

AN XY:

109542

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000108

Gnomad OTH exome

AF:

0.000201

GnomAD4 exome

AF:

0.0178

AC:

15498

AN:

868552

Hom.:

385

Cov.:

AF XY:

0.0193

AC XY:

8314

AN XY:

431762

show subpopulations

Gnomad4 AFR exome

AF:

0.00389

Gnomad4 AMR exome

AF:

0.0500

Gnomad4 ASJ exome

AF:

0.0266

Gnomad4 EAS exome

AF:

0.130

Gnomad4 SAS exome

AF:

0.0299

Gnomad4 FIN exome

AF:

0.0397

Gnomad4 NFE exome

AF:

0.0116

Gnomad4 OTH exome

AF:

0.0184

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00192

AC:

AN:

46302

Hom.:

Cov.:

AF XY:

0.00174

AC XY:

AN XY:

21864

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.00142

Gnomad4 ASJ

AF:

0.00685

Gnomad4 EAS

AF:

0.0121

Gnomad4 SAS

AF:

0.00621

Gnomad4 FIN

AF:

0.00243

Gnomad4 NFE

AF:

0.00200

Gnomad4 OTH

AF:

0.00210

ExAC

AF:

0.00000881

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.023

T;.;T

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.089

LIST_S2

Benign

0.029

T;T;T

M_CAP

Benign

0.0020

MetaRNN

Benign

0.42

T;T;T

MetaSVM

Benign

-0.91

PROVEAN

Pathogenic

-5.8

D;.;D

REVEL

Benign

0.13

Sift

Pathogenic

0.0

D;.;D

Sift4G

Benign

0.077

T;.;D

Polyphen

0.98

D;.;.

Vest4

0.36

MutPred

0.57

Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);.;

MVP

0.23

MPC

0.89

ClinPred

0.96

GERP RS

-3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.63

gMVP

0.19

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