Variant rs17875406 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.873G>A(p.Pro291=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0238 in 1,613,274 control chromosomes in the GnomAD database, including 1,230 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 0.056 ( 513 hom., cov: 30)

Exomes 𝑓: 0.020 ( 717 hom. )

Consequence

HLA-G
NM_001384290.1 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.90

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BP7

Synonymous conserved (PhyloP=-5.9 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.149 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.873G>A	p.Pro291=	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.873G>A	p.Pro291=	synonymous_variant	4/7		NM_001384290.1	ENSP00000353472	P2	P17693-1

Frequencies

GnomAD3 genomes

AF:

0.0562

AC:

8533

AN:

151840

Hom.:

512

Cov.:

show subpopulations

Gnomad AFR

AF:

0.153

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0378

Gnomad ASJ

AF:

0.0306

Gnomad EAS

AF:

0.00213

Gnomad SAS

AF:

0.00767

Gnomad FIN

AF:

0.00226

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0196

Gnomad OTH

AF:

0.0599

GnomAD3 exomes

AF:

0.0247

AC:

6195

AN:

250406

Hom.:

231

AF XY:

0.0219

AC XY:

2964

AN XY:

135514

show subpopulations

Gnomad AFR exome

AF:

0.158

Gnomad AMR exome

AF:

0.0228

Gnomad ASJ exome

AF:

0.0265

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.00902

Gnomad FIN exome

AF:

0.00217

Gnomad NFE exome

AF:

0.0187

Gnomad OTH exome

AF:

0.0265

GnomAD4 exome

AF:

0.0205

AC:

29901

AN:

1461318

Hom.:

717

Cov.:

AF XY:

0.0196

AC XY:

14264

AN XY:

727026

show subpopulations

Gnomad4 AFR exome

AF:

0.161

Gnomad4 AMR exome

AF:

0.0258

Gnomad4 ASJ exome

AF:

0.0255

Gnomad4 EAS exome

AF:

0.000403

Gnomad4 SAS exome

AF:

0.00950

Gnomad4 FIN exome

AF:

0.00285

Gnomad4 NFE exome

AF:

0.0180

Gnomad4 OTH exome

AF:

0.0240

GnomAD4 genome

AF:

0.0562

AC:

8536

AN:

151956

Hom.:

513

Cov.:

AF XY:

0.0535

AC XY:

3975

AN XY:

74270

show subpopulations

Gnomad4 AFR

AF:

0.153

Gnomad4 AMR

AF:

0.0377

Gnomad4 ASJ

AF:

0.0306

Gnomad4 EAS

AF:

0.00214

Gnomad4 SAS

AF:

0.00747

Gnomad4 FIN

AF:

0.00226

Gnomad4 NFE

AF:

0.0196

Gnomad4 OTH

AF:

0.0588

Alfa

AF:

0.0296

Hom.:

Bravo

AF:

0.0645

Asia WGS

AF:

0.0140

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

5.7

DANN

Benign

0.38

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