NM_001384290.1:c.873G>A

Variant names:

• chr6-29829671-G-A
• rs17875406
• NM_001384290.1:c.873G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001384290.1(HLA-G):​c.873G>A​(p.Pro291Pro) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.90
• Publications: 7 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384290.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-G	NM_001384290.1	MANE Select	c.873G>A	p.Pro291Pro	synonymous	Exon 4 of 7	NP_001371219.1
	HLA-G	NM_001363567.2		c.888G>A	p.Pro296Pro	synonymous	Exon 5 of 8	NP_001350496.1
	HLA-G	NM_001384280.1		c.888G>A	p.Pro296Pro	synonymous	Exon 6 of 9	NP_001371209.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-G	ENST00000360323.11	TSL:6 MANE Select	c.873G>A	p.Pro291Pro	synonymous	Exon 4 of 7	ENSP00000353472.6
	HLA-G	ENST00000376828.6	TSL:6	c.888G>A	p.Pro296Pro	synonymous	Exon 5 of 8	ENSP00000366024.2
	HLA-G	ENST00000376818.7	TSL:6	c.597G>A	p.Pro199Pro	synonymous	Exon 3 of 6	ENSP00000366014.3

Frequencies

GnomAD3 genomes AF: 0.0562 AC: 8533 AN: 151840 Hom.: 512 Cov.: 30

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

GnomAD2 exomes AF: 0.0247 AC: 6195 AN: 250406 AF XY: 0.0219

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 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.: 35 AF XY: 0.0196 AC XY: 14264 AN XY: 727026

African (AFR) AF: 0.161 AC: 5372 AN: 33394

American (AMR) AF: 0.0258 AC: 1150 AN: 44528

Ashkenazi Jewish (ASJ) AF: 0.0255 AC: 666 AN: 26118

East Asian (EAS) AF: 0.000403 AC: 16 AN: 39700

South Asian (SAS) AF: 0.00950 AC: 819 AN: 86216

European-Finnish (FIN) AF: 0.00285 AC: 152 AN: 53412

Middle Eastern (MID) AF: 0.0366 AC: 211 AN: 5768

European-Non Finnish (NFE) AF: 0.0180 AC: 20066 AN: 1111826

Other (OTH) AF: 0.0240 AC: 1449 AN: 60356

GnomAD4 genome AF: 0.0562 AC: 8536 AN: 151956 Hom.: 513 Cov.: 30 AF XY: 0.0535 AC XY: 3975 AN XY: 74270

African (AFR) AF: 0.153 AC: 6314 AN: 41396

American (AMR) AF: 0.0377 AC: 576 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0306 AC: 106 AN: 3464

East Asian (EAS) AF: 0.00214 AC: 11 AN: 5152

South Asian (SAS) AF: 0.00747 AC: 36 AN: 4820

European-Finnish (FIN) AF: 0.00226 AC: 24 AN: 10598

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0196 AC: 1334 AN: 67936

Other (OTH) AF: 0.0588 AC: 124 AN: 2110

Alfa AF: 0.0427 Hom.: 262

Bravo AF: 0.0645

Asia WGS AF: 0.0140 AC: 49 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	5.7
DANN	Benign	0.38
PhyloP100		-5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17875406; hg19: chr6-29797448; COSMIC: COSV64406154; COSMIC: COSV64406154;