Variant 6-31356280-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_005514.8(HLA-B):c.506G>A(p.Arg169His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000307 in 1,304,074 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 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. R169L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 6)

Exomes 𝑓: 0.0000031 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HLA-B
NM_005514.8 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.494

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3144065).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-B	NM_005514.8 linkuse as main transcript	c.506G>A	p.Arg169His	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.506G>A	p.Arg169His	missense_variant	3/8		NM_005514.8	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

54242

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000307

AC:

AN:

1304074

Hom.:

Cov.:

AF XY:

0.00000309

AC XY:

AN XY:

647990

show subpopulations

Gnomad4 AFR exome

AF:

0.0000330

Gnomad4 AMR exome

AF:

0.0000523

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.96e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

54242

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

25952

Gnomad4 AFR

AF:

0.00

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:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000827

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.017

T;.;T

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.050

T;T;T

M_CAP

Benign

0.0028

MetaRNN

Benign

0.31

T;T;T

MetaSVM

Benign

-0.96

MutationTaster

Benign

1.0

PROVEAN

Uncertain

-3.0

D;.;D

REVEL

Benign

0.084

Sift

Pathogenic

0.0

D;.;D

Sift4G

Benign

0.10

T;.;D

Polyphen

0.97

D;.;.

Vest4

0.24

MutPred

0.66

Loss of MoRF binding (P = 0.011);Loss of MoRF binding (P = 0.011);.;

MVP

0.17

MPC

0.93

ClinPred

0.91

GERP RS

0.27

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.41

gMVP

0.16

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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