Variant rs4997052 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005514.8(HLA-B):c.419A>T(p.Tyr140Phe) 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. Y140D) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.041 ( 24 hom., cov: 3)

Exomes 𝑓: 0.15 ( 12826 hom. )

Failed GnomAD Quality Control

Consequence

HLA-B
NM_005514.8 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -8.15

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008739829).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-B	NM_005514.8 linkuse as main transcript	c.419A>T	p.Tyr140Phe	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.419A>T	p.Tyr140Phe	missense_variant	3/8		NM_005514.8	ENSP00000399168	P1

Frequencies

GnomAD3 genomes

AF:

0.0412

AC:

1449

AN:

35150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0457

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0485

Gnomad ASJ

AF:

0.200

Gnomad EAS

AF:

0.117

Gnomad SAS

AF:

0.217

Gnomad FIN

AF:

0.0197

Gnomad MID

AF:

0.188

Gnomad NFE

AF:

0.0267

Gnomad OTH

AF:

0.0650

GnomAD3 exomes

AF:

0.194

AC:

36537

AN:

187878

Hom.:

3149

AF XY:

0.195

AC XY:

19958

AN XY:

102434

show subpopulations

Gnomad AFR exome

AF:

0.157

Gnomad AMR exome

AF:

0.281

Gnomad ASJ exome

AF:

0.446

Gnomad EAS exome

AF:

0.207

Gnomad SAS exome

AF:

0.234

Gnomad FIN exome

AF:

0.152

Gnomad NFE exome

AF:

0.145

Gnomad OTH exome

AF:

0.206

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.150

AC:

127416

AN:

850382

Hom.:

12826

Cov.:

AF XY:

0.156

AC XY:

66620

AN XY:

426726

show subpopulations

Gnomad4 AFR exome

AF:

0.175

Gnomad4 AMR exome

AF:

0.217

Gnomad4 ASJ exome

AF:

0.355

Gnomad4 EAS exome

AF:

0.147

Gnomad4 SAS exome

AF:

0.278

Gnomad4 FIN exome

AF:

0.104

Gnomad4 NFE exome

AF:

0.132

Gnomad4 OTH exome

AF:

0.165

GnomAD4 genome

AF:

0.0414

AC:

1454

AN:

35160

Hom.:

Cov.:

AF XY:

0.0419

AC XY:

698

AN XY:

16668

show subpopulations

Gnomad4 AFR

AF:

0.0459

Gnomad4 AMR

AF:

0.0490

Gnomad4 ASJ

AF:

0.200

Gnomad4 EAS

AF:

0.118

Gnomad4 SAS

AF:

0.214

Gnomad4 FIN

AF:

0.0197

Gnomad4 NFE

AF:

0.0267

Gnomad4 OTH

AF:

0.0746

Alfa

AF:

0.183

Hom.:

295

ExAC

AF:

0.202

AC:

24019

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.59

CADD

Benign

0.0020

DANN

Benign

0.28

DEOGEN2

Benign

0.019

T;.;T

Eigen

Benign

-3.3

Eigen_PC

Benign

-3.3

FATHMM_MKL

Benign

0.0038

LIST_S2

Benign

0.0094

T;T;T

MetaRNN

Benign

0.0087

T;T;T

MetaSVM

Benign

-0.97

MutationTaster

Benign

1.0

PROVEAN

Benign

-0.60

N;.;N

REVEL

Benign

0.23

Sift

Benign

0.55

T;.;T

Sift4G

Benign

1.0

T;.;T

Polyphen

0.0

B;.;.

Vest4

0.079

MPC

0.20

ClinPred

0.0062

GERP RS

-6.4

Varity_R

0.22

gMVP

0.058

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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