Variant rs1130355 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.243G>A(p.Pro81Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 1,612,856 control chromosomes in the GnomAD database, including 191,972 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 0.49 ( 18141 hom., cov: 32)

Exomes 𝑓: 0.48 ( 173831 hom. )

Consequence

HLA-G
NM_001384290.1 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.738

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:

HCG4P8 (HGNC:22927): (HLA complex group 4 pseudogene 8)

HCG4P8 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=-0.54).

BP7

Synonymous conserved (PhyloP=0.738 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-G	NM_001384290.1 link	c.243G>A	p.Pro81Pro	synonymous_variant	2/7	ENST00000360323.11	NP_001371219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-G	ENST00000360323.11 link	c.243G>A	p.Pro81Pro	synonymous_variant	2/7	6	NM_001384290.1	ENSP00000353472.6		P17693-1

Frequencies

GnomAD3 genomes

AF:

0.485

AC:

73698

AN:

151894

Hom.:

18118

Cov.:

show subpopulations

Gnomad AFR

AF:

0.510

Gnomad AMI

AF:

0.463

Gnomad AMR

AF:

0.515

Gnomad ASJ

AF:

0.568

Gnomad EAS

AF:

0.613

Gnomad SAS

AF:

0.666

Gnomad FIN

AF:

0.339

Gnomad MID

AF:

0.589

Gnomad NFE

AF:

0.459

Gnomad OTH

AF:

0.500

GnomAD3 exomes

AF:

0.497

AC:

123031

AN:

247652

Hom.:

31967

AF XY:

0.507

AC XY:

68183

AN XY:

134596

show subpopulations

Gnomad AFR exome

AF:

0.511

Gnomad AMR exome

AF:

0.499

Gnomad ASJ exome

AF:

0.575

Gnomad EAS exome

AF:

0.599

Gnomad SAS exome

AF:

0.675

Gnomad FIN exome

AF:

0.337

Gnomad NFE exome

AF:

0.452

Gnomad OTH exome

AF:

0.496

GnomAD4 exome

AF:

0.482

AC:

703673

AN:

1460844

Hom.:

173831

Cov.:

AF XY:

0.489

AC XY:

355187

AN XY:

726726

show subpopulations

Gnomad4 AFR exome

AF:

0.512

Gnomad4 AMR exome

AF:

0.504

Gnomad4 ASJ exome

AF:

0.574

Gnomad4 EAS exome

AF:

0.655

Gnomad4 SAS exome

AF:

0.672

Gnomad4 FIN exome

AF:

0.344

Gnomad4 NFE exome

AF:

0.461

Gnomad4 OTH exome

AF:

0.512

GnomAD4 genome

AF:

0.485

AC:

73762

AN:

152012

Hom.:

18141

Cov.:

AF XY:

0.485

AC XY:

36043

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.510

Gnomad4 AMR

AF:

0.514

Gnomad4 ASJ

AF:

0.568

Gnomad4 EAS

AF:

0.612

Gnomad4 SAS

AF:

0.666

Gnomad4 FIN

AF:

0.339

Gnomad4 NFE

AF:

0.459

Gnomad4 OTH

AF:

0.505

Alfa

AF:

0.479

Hom.:

7617

Bravo

AF:

0.496

Asia WGS

AF:

0.685

AC:

2383

AN:

3478

EpiCase

AF:

0.490

EpiControl

AF:

0.478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.92

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