rs17875402

chr6-29828715-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BS1 BS2

The NM_001384290.1(HLA-G):c.516G>A(p.Glu172=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000915 in 1,613,868 control chromosomes in the GnomAD database, including 11 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 0.0048 (7 hom., cov: 32)
  • Exomes 𝑓: 0.00051 (4 hom.)
• Consequence: HLA-G NM_001384290.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.129

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

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP7: Synonymous conserved (PhyloP=0.129 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00484 (737/152350) while in subpopulation AFR AF= 0.0164 (681/41578). AF 95% confidence interval is 0.0154. There are 7 homozygotes in gnomad4. There are 337 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-G	NM_001384290.1	c.516G>A	p.Glu172=	synonymous_variant	3/7	ENST00000360323.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-G	ENST00000360323.11	c.516G>A	p.Glu172=	synonymous_variant	3/7		NM_001384290.1	P2

Frequencies

GnomAD3 genomes AF: 0.00483 AC: 735 AN: 152232 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.0164

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00301

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00431

GnomAD3 exomes AF: 0.00109 AC: 272 AN: 248636 Hom.: 0 AF XY: 0.000800 AC XY: 108 AN XY: 134938

Gnomad AFR exome AF: 0.0152

Gnomad AMR exome AF: 0.000781

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000268

Gnomad OTH exome AF: 0.000492

GnomAD4 exome AF: 0.000506 AC: 740 AN: 1461518 Hom.: 4 Cov.: 46 AF XY: 0.000404 AC XY: 294 AN XY: 727072

Gnomad4 AFR exome AF: 0.0184

Gnomad4 AMR exome AF: 0.000760

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000812

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000719

Gnomad4 OTH exome AF: 0.00109

GnomAD4 genome AF: 0.00484 AC: 737 AN: 152350 Hom.: 7 Cov.: 32 AF XY: 0.00452 AC XY: 337 AN XY: 74512

Gnomad4 AFR AF: 0.0164

Gnomad4 AMR AF: 0.00300

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00133 Hom.: 2

Bravo AF: 0.00525

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	8.5
Dann	Benign	0.76

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

Other links and lift over

dbSNP: rs17875402; hg19: chr6-29796492;