Variant 6-29829434-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001384290.1(HLA-G):c.636C>T(p.His212His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0398 in 1,613,360 control chromosomes in the GnomAD database, including 1,733 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 0.058 ( 368 hom., cov: 30)

Exomes 𝑓: 0.038 ( 1365 hom. )

Consequence

HLA-G
NM_001384290.1 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.85

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:

HLA-G (HGNC:):

HLA-G links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP7

Synonymous conserved (PhyloP=-2.85 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.101 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.636C>T	p.His212His	synonymous_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.636C>T	p.His212His	synonymous_variant	4/7	6	NM_001384290.1	ENSP00000353472.6		P17693-1

Frequencies

GnomAD3 genomes

AF:

0.0576

AC:

8754

AN:

151950

Hom.:

362

Cov.:

show subpopulations

Gnomad AFR

AF:

0.103

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0850

Gnomad ASJ

AF:

0.0772

Gnomad EAS

AF:

0.00753

Gnomad SAS

AF:

0.0286

Gnomad FIN

AF:

0.0106

Gnomad MID

AF:

0.0987

Gnomad NFE

AF:

0.0361

Gnomad OTH

AF:

0.0724

GnomAD3 exomes

AF:

0.0456

AC:

11424

AN:

250700

Hom.:

400

AF XY:

0.0427

AC XY:

5788

AN XY:

135462

show subpopulations

Gnomad AFR exome

AF:

0.104

Gnomad AMR exome

AF:

0.0936

Gnomad ASJ exome

AF:

0.0757

Gnomad EAS exome

AF:

0.00386

Gnomad SAS exome

AF:

0.0375

Gnomad FIN exome

AF:

0.0117

Gnomad NFE exome

AF:

0.0351

Gnomad OTH exome

AF:

0.0495

GnomAD4 exome

AF:

0.0379

AC:

55421

AN:

1461292

Hom.:

1365

Cov.:

AF XY:

0.0376

AC XY:

27361

AN XY:

726950

show subpopulations

Gnomad4 AFR exome

AF:

0.104

Gnomad4 AMR exome

AF:

0.0943

Gnomad4 ASJ exome

AF:

0.0772

Gnomad4 EAS exome

AF:

0.00713

Gnomad4 SAS exome

AF:

0.0376

Gnomad4 FIN exome

AF:

0.0126

Gnomad4 NFE exome

AF:

0.0345

Gnomad4 OTH exome

AF:

0.0436

GnomAD4 genome

AF:

0.0577

AC:

8774

AN:

152068

Hom.:

368

Cov.:

AF XY:

0.0550

AC XY:

4088

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.103

Gnomad4 AMR

AF:

0.0856

Gnomad4 ASJ

AF:

0.0772

Gnomad4 EAS

AF:

0.00755

Gnomad4 SAS

AF:

0.0291

Gnomad4 FIN

AF:

0.0106

Gnomad4 NFE

AF:

0.0361

Gnomad4 OTH

AF:

0.0716

Alfa

AF:

0.0359

Hom.:

Bravo

AF:

0.0671

Asia WGS

AF:

0.0270

AC:

AN:

3478

EpiCase

AF:

0.0385

EpiControl

AF:

0.0411

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.12

DANN

Benign

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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