rs1710

Positions:

• chr6-29830840-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001384290.1(HLA-G):​c.*101G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 151,762 control chromosomes in the GnomAD database, including 22,787 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 (22787 hom., cov: 30)
  • Exomes 𝑓: 0.62 (54280 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-G NM_001384290.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.735

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• 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/exons	MANE	Protein	UniProt
HLA-G	NM_001384290.1	c.*101G>C		3_prime_UTR_variant	7/7	ENST00000360323.11	NP_001371219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-G	ENST00000360323.11	c.*101G>C		3_prime_UTR_variant	7/7		NM_001384290.1	ENSP00000353472	P2

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82321 AN: 151644 Hom.: 22753 Cov.: 30

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.461

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.644

Gnomad EAS AF: 0.621

Gnomad SAS AF: 0.695

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.571

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.616 AC: 168694 AN: 273636 Hom.: 54280 Cov.: 0 AF XY: 0.634 AC XY: 98692 AN XY: 155550

Gnomad4 AFR exome AF: 0.672

Gnomad4 AMR exome AF: 0.688

Gnomad4 ASJ exome AF: 0.752

Gnomad4 EAS exome AF: 0.626

Gnomad4 SAS exome AF: 0.777

Gnomad4 FIN exome AF: 0.432

Gnomad4 NFE exome AF: 0.548

Gnomad4 OTH exome AF: 0.596

GnomAD4 genome AF: 0.543 AC: 82405 AN: 151762 Hom.: 22787 Cov.: 30 AF XY: 0.540 AC XY: 40077 AN XY: 74162

Gnomad4 AFR AF: 0.614

Gnomad4 AMR AF: 0.600

Gnomad4 ASJ AF: 0.644

Gnomad4 EAS AF: 0.620

Gnomad4 SAS AF: 0.696

Gnomad4 FIN AF: 0.351

Gnomad4 NFE AF: 0.495

Gnomad4 OTH AF: 0.576

Alfa AF: 0.514 Hom.: 2503

Bravo AF: 0.563

Asia WGS AF: 0.710 AC: 2469 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	13
DANN	Benign	0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.20		Position offset: 6

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1710; hg19: chr6-29798617; COSMIC: COSV64407083; COSMIC: COSV64407083;