Variant 6-31356389-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBS2_Supporting

The NM_005514.8(HLA-B):c.397C>T(p.Leu133Phe) 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. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00010 ( 0 hom., cov: 5)

Exomes 𝑓: 0.0010 ( 9 hom. )

Consequence

HLA-B
NM_005514.8 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.457

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 -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008583397).

BP6

Variant 6-31356389-G-A is Benign according to our data. Variant chr6-31356389-G-A is described in ClinVar as [Benign]. Clinvar id is 2656393.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 5 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-B	NM_005514.8 linkuse as main transcript	c.397C>T	p.Leu133Phe	missense_variant	3/8	ENST00000412585.7	NP_005505.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-B	ENST00000412585.7 linkuse as main transcript	c.397C>T	p.Leu133Phe	missense_variant	3/8		NM_005514.8	ENSP00000399168	P1

Frequencies

GnomAD3 genomes

AF:

0.000104

AC:

AN:

48088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000519

Gnomad ASJ

AF:

0.00217

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000795

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00698

AC:

1616

AN:

231652

Hom.:

AF XY:

0.00734

AC XY:

930

AN XY:

126630

show subpopulations

Gnomad AFR exome

AF:

0.000609

Gnomad AMR exome

AF:

0.00731

Gnomad ASJ exome

AF:

0.0650

Gnomad EAS exome

AF:

0.000227

Gnomad SAS exome

AF:

0.00599

Gnomad FIN exome

AF:

0.000786

Gnomad NFE exome

AF:

0.00506

Gnomad OTH exome

AF:

0.0123

GnomAD4 exome

AF:

0.00101

AC:

967

AN:

960554

Hom.:

Cov.:

AF XY:

0.00106

AC XY:

506

AN XY:

477726

show subpopulations

Gnomad4 AFR exome

AF:

0.00301

Gnomad4 AMR exome

AF:

0.00189

Gnomad4 ASJ exome

AF:

0.0214

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00180

Gnomad4 FIN exome

AF:

0.000202

Gnomad4 NFE exome

AF:

0.000544

Gnomad4 OTH exome

AF:

0.00210

GnomAD4 genome

AF:

0.000104

AC:

AN:

48108

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

22900

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000518

Gnomad4 ASJ

AF:

0.00217

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000795

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0111

Hom.:

ESP6500AA

AF:

0.00149

AC:

ESP6500EA

AF:

0.00531

AC:

ExAC

AF:

0.00773

AC:

917

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2024

HLA-B: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.025

T;.;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.36

T;T;T

MetaRNN

Benign

0.0086

T;T;T

MetaSVM

Benign

-0.97

MutationTaster

Benign

1.0

PROVEAN

Benign

-2.3

N;.;N

REVEL

Benign

0.14

Sift

Benign

0.12

T;.;D

Sift4G

Benign

0.29

T;.;T

Polyphen

0.0050

B;.;.

Vest4

0.17

MVP

0.014

MPC

0.24

ClinPred

0.0033

GERP RS

-2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.25

gMVP

0.027

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over