Variant 6-29829643-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001384290.1(HLA-G):c.845C>T(p.Thr282Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0598 in 1,613,874 control chromosomes in the GnomAD database, including 3,630 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.

Frequency

Genomes: 𝑓 0.044 ( 217 hom., cov: 30)

Exomes 𝑓: 0.061 ( 3413 hom. )

Consequence

HLA-G
NM_001384290.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.716

Variant links:

Genes affected

HLA-G (HGNC:4964): (major histocompatibility complex, class I, G) HLA-G 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-G is expressed on fetal derived placental cells. 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 domain, which both bind the peptide, exon 4 encodes the alpha3 domain, exon 5 encodes the transmembrane region, and exon 6 encodes the cytoplasmic tail. [provided by RefSeq, Jul 2008]

HLA-G 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=0.0069839656).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-G	NM_001384290.1 linkuse as main transcript	c.845C>T	p.Thr282Met	missense_variant	4/7	ENST00000360323.11	NP_001371219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-G	ENST00000360323.11 linkuse as main transcript	c.845C>T	p.Thr282Met	missense_variant	4/7		NM_001384290.1	ENSP00000353472	P2	P17693-1

Frequencies

GnomAD3 genomes

AF:

0.0440

AC:

6683

AN:

151940

Hom.:

217

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0137

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.0423

Gnomad ASJ

AF:

0.0938

Gnomad EAS

AF:

0.0149

Gnomad SAS

AF:

0.124

Gnomad FIN

AF:

0.0245

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.0594

Gnomad OTH

AF:

0.0565

GnomAD3 exomes

AF:

0.0566

AC:

14216

AN:

251030

Hom.:

575

AF XY:

0.0623

AC XY:

8452

AN XY:

135714

show subpopulations

Gnomad AFR exome

AF:

0.0114

Gnomad AMR exome

AF:

0.0358

Gnomad ASJ exome

AF:

0.0995

Gnomad EAS exome

AF:

0.00870

Gnomad SAS exome

AF:

0.134

Gnomad FIN exome

AF:

0.0206

Gnomad NFE exome

AF:

0.0590

Gnomad OTH exome

AF:

0.0669

GnomAD4 exome

AF:

0.0615

AC:

89856

AN:

1461816

Hom.:

3413

Cov.:

AF XY:

0.0642

AC XY:

46667

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.0127

Gnomad4 AMR exome

AF:

0.0361

Gnomad4 ASJ exome

AF:

0.0989

Gnomad4 EAS exome

AF:

0.00753

Gnomad4 SAS exome

AF:

0.132

Gnomad4 FIN exome

AF:

0.0228

Gnomad4 NFE exome

AF:

0.0609

Gnomad4 OTH exome

AF:

0.0660

GnomAD4 genome

AF:

0.0439

AC:

6676

AN:

152058

Hom.:

217

Cov.:

AF XY:

0.0447

AC XY:

3319

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.0136

Gnomad4 AMR

AF:

0.0422

Gnomad4 ASJ

AF:

0.0938

Gnomad4 EAS

AF:

0.0150

Gnomad4 SAS

AF:

0.124

Gnomad4 FIN

AF:

0.0245

Gnomad4 NFE

AF:

0.0594

Gnomad4 OTH

AF:

0.0564

Alfa

AF:

0.0553

Hom.:

131

Bravo

AF:

0.0425

TwinsUK

AF:

0.0515

AC:

191

ALSPAC

AF:

0.0560

AC:

216

ESP6500AA

AF:

0.0148

AC:

ESP6500EA

AF:

0.0633

AC:

544

ExAC

AF:

0.0572

AC:

6942

Asia WGS

AF:

0.0580

AC:

205

AN:

3478

EpiCase

AF:

0.0674

EpiControl

AF:

0.0659

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.059

.;T;T;T

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.34

T;T;.;.

MetaRNN

Benign

0.0070

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.5

.;M;M;.

MutationTaster

Benign

1.0

D;N;N;N;N

PrimateAI

Benign

0.24

PROVEAN

Uncertain

-3.3

D;D;D;D

REVEL

Benign

0.11

Sift

Uncertain

0.0090

D;D;D;D

Sift4G

Uncertain

0.036

D;D;D;D

Polyphen

1.0

D;D;D;D

Vest4

0.074

MPC

1.4

ClinPred

0.052

GERP RS

0.31

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.067

gMVP

0.35

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