Variant rs1264457 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_005516.6(HLA-E):c.382G>A(p.Gly128Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 1,612,602 control chromosomes in the GnomAD database, including 269,031 homozygotes. In-silico tool predicts 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.

Frequency

Genomes: 𝑓 0.55 ( 23420 hom., cov: 32)

Exomes 𝑓: 0.58 ( 245611 hom. )

Consequence

HLA-E
NM_005516.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.02

Variant links:

Genes affected

HLA-E (HGNC:4962): (major histocompatibility complex, class I, E) HLA-E 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. HLA-E binds a restricted subset of peptides derived from the leader peptides of other class I molecules. The heavy chain is approximately 45 kDa and its gene contains 8 exons. Exon one encodes the leader peptide, exons 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. [provided by RefSeq, Jul 2008]

HLA-E links:

HLA-E (HGNC:):

HLA-E links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-E	NM_005516.6 linkuse as main transcript	c.382G>A	p.Gly128Arg	missense_variant	3/8	ENST00000376630.5	NP_005507.3	P13747A0A4E9D3W4A8K8M6O19682
HLA-E	XM_017010807.2 linkuse as main transcript	c.505G>A	p.Gly169Arg	missense_variant	2/7		XP_016866296.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
HLA-E	ENST00000376630.5 linkuse as main transcript	c.382G>A	p.Gly128Arg	missense_variant	3/8	6	NM_005516.6	ENSP00000365817.4	P13747
HLA-E	ENST00000484194.1 linkuse as main transcript	n.648G>A		non_coding_transcript_exon_variant	2/2	6
HLA-E	ENST00000493699.1 linkuse as main transcript	n.532G>A		non_coding_transcript_exon_variant	2/3	6

Frequencies

GnomAD3 genomes

AF:

0.553

AC:

83970

AN:

151902

Hom.:

23409

Cov.:

show subpopulations

Gnomad AFR

AF:

0.567

Gnomad AMI

AF:

0.641

Gnomad AMR

AF:

0.524

Gnomad ASJ

AF:

0.543

Gnomad EAS

AF:

0.370

Gnomad SAS

AF:

0.543

Gnomad FIN

AF:

0.484

Gnomad MID

AF:

0.595

Gnomad NFE

AF:

0.575

Gnomad OTH

AF:

0.544

GnomAD3 exomes

AF:

0.539

AC:

133033

AN:

246762

Hom.:

36372

AF XY:

0.541

AC XY:

72835

AN XY:

134592

show subpopulations

Gnomad AFR exome

AF:

0.565

Gnomad AMR exome

AF:

0.548

Gnomad ASJ exome

AF:

0.541

Gnomad EAS exome

AF:

0.378

Gnomad SAS exome

AF:

0.542

Gnomad FIN exome

AF:

0.485

Gnomad NFE exome

AF:

0.569

Gnomad OTH exome

AF:

0.544

GnomAD4 exome

AF:

0.577

AC:

843086

AN:

1460580

Hom.:

245611

Cov.:

AF XY:

0.576

AC XY:

418743

AN XY:

726594

show subpopulations

Gnomad4 AFR exome

AF:

0.575

Gnomad4 AMR exome

AF:

0.549

Gnomad4 ASJ exome

AF:

0.554

Gnomad4 EAS exome

AF:

0.358

Gnomad4 SAS exome

AF:

0.550

Gnomad4 FIN exome

AF:

0.493

Gnomad4 NFE exome

AF:

0.593

Gnomad4 OTH exome

AF:

0.580

GnomAD4 genome

AF:

0.553

AC:

84013

AN:

152022

Hom.:

23420

Cov.:

AF XY:

0.544

AC XY:

40424

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.567

Gnomad4 AMR

AF:

0.524

Gnomad4 ASJ

AF:

0.543

Gnomad4 EAS

AF:

0.370

Gnomad4 SAS

AF:

0.543

Gnomad4 FIN

AF:

0.484

Gnomad4 NFE

AF:

0.575

Gnomad4 OTH

AF:

0.537

Alfa

AF:

0.555

Hom.:

12179

Bravo

AF:

0.561

TwinsUK

AF:

0.599

AC:

2221

ALSPAC

AF:

0.591

AC:

2278

ESP6500AA

AF:

0.560

AC:

1690

ESP6500EA

AF:

0.568

AC:

3076

ExAC

AF:

0.535

AC:

63685

Asia WGS

AF:

0.448

AC:

1558

AN:

3478

EpiCase

AF:

0.577

EpiControl

AF:

0.569

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.76

CADD

Uncertain

DANN

Benign

0.97

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.019

MetaRNN

Benign

0.00011

MetaSVM

Benign

-1.3

PrimateAI

Benign

0.31

PROVEAN

Pathogenic

-6.3

REVEL

Benign

0.065

Sift

Benign

0.051

Sift4G

Uncertain

0.058

Vest4

0.21

MutPred

0.73

Loss of methylation at R129 (P = 0.0423);

MPC

0.93

ClinPred

0.034

GERP RS

0.76

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Varity_R

0.24

gMVP

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.52

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.52

Position offset: 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