6-29829919-A-G

Variant names:

• chr6-29829919-A-G
• rs1130363
• NM_001384290.1:c.999A>G

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.999A>G​(p.Arg333Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 1,608,058 control chromosomes in the GnomAD database, including 224,642 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 0.54 (22815 hom., cov: 30)
  • Exomes 𝑓: 0.52 (201827 hom.)
• Consequence: HLA-G NM_001384290.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.746
• Publications: 26 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=-1.06).
• BP7: Synonymous conserved (PhyloP=-0.746 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-G	NM_001384290.1	c.999A>G	p.Arg333Arg	synonymous_variant	Exon 5 of 7	ENST00000360323.11	NP_001371219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-G	ENST00000360323.11	c.999A>G	p.Arg333Arg	synonymous_variant	Exon 5 of 7	6	NM_001384290.1	ENSP00000353472.6

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82378 AN: 151590 Hom.: 22781 Cov.: 30

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.620

Gnomad SAS AF: 0.695

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.685

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.574

GnomAD2 exomes AF: 0.544 AC: 135687 AN: 249572 AF XY: 0.550

Gnomad AFR exome AF: 0.618

Gnomad AMR exome AF: 0.593

Gnomad ASJ exome AF: 0.652

Gnomad EAS exome AF: 0.603

Gnomad FIN exome AF: 0.349

Gnomad NFE exome AF: 0.490

Gnomad OTH exome AF: 0.546

GnomAD4 exome AF: 0.520 AC: 756638 AN: 1456350 Hom.: 201827 Cov.: 33 AF XY: 0.526 AC XY: 381478 AN XY: 724772

African (AFR) AF: 0.615 AC: 20483 AN: 33288

American (AMR) AF: 0.598 AC: 26482 AN: 44284

Ashkenazi Jewish (ASJ) AF: 0.651 AC: 16938 AN: 26018

East Asian (EAS) AF: 0.662 AC: 26290 AN: 39694

South Asian (SAS) AF: 0.709 AC: 61037 AN: 86036

European-Finnish (FIN) AF: 0.359 AC: 19160 AN: 53388

Middle Eastern (MID) AF: 0.650 AC: 3736 AN: 5750

European-Non Finnish (NFE) AF: 0.496 AC: 549061 AN: 1107694

Other (OTH) AF: 0.556 AC: 33451 AN: 60198

GnomAD4 genome AF: 0.544 AC: 82462 AN: 151708 Hom.: 22815 Cov.: 30 AF XY: 0.541 AC XY: 40070 AN XY: 74066

African (AFR) AF: 0.614 AC: 25399 AN: 41350

American (AMR) AF: 0.601 AC: 9169 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.645 AC: 2236 AN: 3464

East Asian (EAS) AF: 0.619 AC: 3171 AN: 5126

South Asian (SAS) AF: 0.696 AC: 3340 AN: 4802

European-Finnish (FIN) AF: 0.351 AC: 3687 AN: 10498

Middle Eastern (MID) AF: 0.675 AC: 197 AN: 292

European-Non Finnish (NFE) AF: 0.495 AC: 33626 AN: 67898

Other (OTH) AF: 0.578 AC: 1216 AN: 2102

Alfa AF: 0.539 Hom.: 10856

Bravo AF: 0.563

Asia WGS AF: 0.712 AC: 2475 AN: 3478

EpiCase AF: 0.528

EpiControl AF: 0.518

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	5.8
DANN	Benign	0.60
PhyloP100		-0.75
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1130363; hg19: chr6-29797696; COSMIC: COSV64406454; COSMIC: COSV64406454;