rs915670

Positions:

• chr6-29830642-G-A
• chr6-29830642-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.*29-126G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 698,732 control chromosomes in the GnomAD database, including 27,959 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 0.27 (5482 hom., cov: 31)
  • Exomes 𝑓: 0.28 (22477 hom.)
• Consequence: HLA-G NM_001384290.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.03

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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-G	NM_001384290.1	c.*29-126G>A		intron_variant		ENST00000360323.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-G	ENST00000360323.11	c.*29-126G>A		intron_variant			NM_001384290.1	P2

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40537 AN: 151938 Hom.: 5480 Cov.: 31

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.272

GnomAD4 exome AF: 0.278 AC: 152160 AN: 546678 Hom.: 22477 Cov.: 2 AF XY: 0.282 AC XY: 83865 AN XY: 297218

Gnomad4 AFR exome AF: 0.264

Gnomad4 AMR exome AF: 0.285

Gnomad4 ASJ exome AF: 0.385

Gnomad4 EAS exome AF: 0.152

Gnomad4 SAS exome AF: 0.303

Gnomad4 FIN exome AF: 0.203

Gnomad4 NFE exome AF: 0.292

Gnomad4 OTH exome AF: 0.281

GnomAD4 genome AF: 0.267 AC: 40560 AN: 152054 Hom.: 5482 Cov.: 31 AF XY: 0.262 AC XY: 19515 AN XY: 74350

Gnomad4 AFR AF: 0.257

Gnomad4 AMR AF: 0.276

Gnomad4 ASJ AF: 0.381

Gnomad4 EAS AF: 0.109

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.193

Gnomad4 NFE AF: 0.289

Gnomad4 OTH AF: 0.268

Alfa AF: 0.288 Hom.: 777

Bravo AF: 0.273

Asia WGS AF: 0.178 AC: 625 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.5
DANN	Benign	0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs915670; hg19: chr6-29798419; COSMIC: COSV64405045; COSMIC: COSV64405045;