Variant chr6-29828550-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.351C>T(p.His117=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 1,612,148 control chromosomes in the GnomAD database, including 80,020 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 0.28 ( 6277 hom., cov: 32)

Exomes 𝑓: 0.31 ( 73743 hom. )

Consequence

HLA-G
NM_001384290.1 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.322

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.307 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.351C>T	p.His117=	synonymous_variant	3/7	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.351C>T	p.His117=	synonymous_variant	3/7		NM_001384290.1	ENSP00000353472	P2	P17693-1

Frequencies

GnomAD3 genomes

AF:

0.285

AC:

43228

AN:

151900

Hom.:

6273

Cov.:

show subpopulations

Gnomad AFR

AF:

0.269

Gnomad AMI

AF:

0.258

Gnomad AMR

AF:

0.289

Gnomad ASJ

AF:

0.400

Gnomad EAS

AF:

0.112

Gnomad SAS

AF:

0.296

Gnomad FIN

AF:

0.212

Gnomad MID

AF:

0.377

Gnomad NFE

AF:

0.311

Gnomad OTH

AF:

0.288

GnomAD3 exomes

AF:

0.284

AC:

70029

AN:

246148

Hom.:

10721

AF XY:

0.290

AC XY:

38958

AN XY:

134220

show subpopulations

Gnomad AFR exome

AF:

0.265

Gnomad AMR exome

AF:

0.283

Gnomad ASJ exome

AF:

0.404

Gnomad EAS exome

AF:

0.0929

Gnomad SAS exome

AF:

0.336

Gnomad FIN exome

AF:

0.211

Gnomad NFE exome

AF:

0.308

Gnomad OTH exome

AF:

0.295

GnomAD4 exome

AF:

0.314

AC:

457897

AN:

1460130

Hom.:

73743

Cov.:

AF XY:

0.316

AC XY:

229315

AN XY:

726326

show subpopulations

Gnomad4 AFR exome

AF:

0.268

Gnomad4 AMR exome

AF:

0.286

Gnomad4 ASJ exome

AF:

0.403

Gnomad4 EAS exome

AF:

0.154

Gnomad4 SAS exome

AF:

0.337

Gnomad4 FIN exome

AF:

0.218

Gnomad4 NFE exome

AF:

0.322

Gnomad4 OTH exome

AF:

0.314

GnomAD4 genome

AF:

0.285

AC:

43257

AN:

152018

Hom.:

6277

Cov.:

AF XY:

0.280

AC XY:

20772

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.269

Gnomad4 AMR

AF:

0.289

Gnomad4 ASJ

AF:

0.400

Gnomad4 EAS

AF:

0.113

Gnomad4 SAS

AF:

0.296

Gnomad4 FIN

AF:

0.212

Gnomad4 NFE

AF:

0.311

Gnomad4 OTH

AF:

0.284

Alfa

AF:

0.310

Hom.:

3502

Bravo

AF:

0.290

Asia WGS

AF:

0.191

AC:

668

AN:

3478

EpiCase

AF:

0.331

EpiControl

AF:

0.318

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.87

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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