rs1632947

Positions:

• chr6-29826881-G-A

Variant summary

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

The NM_001384280.1(HLA-G):​c.-36-122G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 422,470 control chromosomes in the GnomAD database, including 53,524 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 0.49 (18125 hom., cov: 31)
  • Exomes 𝑓: 0.50 (35399 hom.)
• Consequence: HLA-G NM_001384280.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.653

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-G	NM_001384280.1	c.-36-122G>A		intron_variant			NP_001371209.1
		n.29826881G>A		intergenic_region
HCG4P8		n.29826881G>A		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73664 AN: 151810 Hom.: 18102 Cov.: 31

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.567

Gnomad EAS AF: 0.612

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.586

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.501

GnomAD4 exome AF: 0.499 AC: 135035 AN: 270542 Hom.: 35399 AF XY: 0.520 AC XY: 78373 AN XY: 150812

Gnomad4 AFR exome AF: 0.508

Gnomad4 AMR exome AF: 0.502

Gnomad4 ASJ exome AF: 0.564

Gnomad4 EAS exome AF: 0.602

Gnomad4 SAS exome AF: 0.666

Gnomad4 FIN exome AF: 0.342

Gnomad4 NFE exome AF: 0.452

Gnomad4 OTH exome AF: 0.495

GnomAD4 genome AF: 0.485 AC: 73727 AN: 151928 Hom.: 18125 Cov.: 31 AF XY: 0.485 AC XY: 36043 AN XY: 74260

Gnomad4 AFR AF: 0.510

Gnomad4 AMR AF: 0.515

Gnomad4 ASJ AF: 0.567

Gnomad4 EAS AF: 0.611

Gnomad4 SAS AF: 0.665

Gnomad4 FIN AF: 0.341

Gnomad4 NFE AF: 0.459

Gnomad4 OTH AF: 0.507

Alfa AF: 0.470 Hom.: 2083

Bravo AF: 0.496

Asia WGS AF: 0.683 AC: 2375 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.97
DANN	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1632947; hg19: chr6-29794658; COSMIC: COSV64405568;