rs915667

Positions:

• chr6-29830363-A-G
• chr6-29830363-A-T

Variant summary

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

The NM_001384290.1(HLA-G):​c.1013-15A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 1,609,026 control chromosomes in the GnomAD database, including 176,925 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 0.47 (16911 hom., cov: 31)
  • Exomes 𝑓: 0.46 (160014 hom.)
• Consequence: HLA-G NM_001384290.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94

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]

HLA-G (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.617 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-G	NM_001384290.1	c.1013-15A>G		intron_variant		ENST00000360323.11	NP_001371219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-G	ENST00000360323.11	c.1013-15A>G		intron_variant		6	NM_001384290.1	ENSP00000353472.6

Frequencies

GnomAD3 genomes AF: 0.469 AC: 71143 AN: 151748 Hom.: 16893 Cov.: 31

Gnomad AFR AF: 0.500

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.550

Gnomad EAS AF: 0.604

Gnomad SAS AF: 0.635

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.483

GnomAD3 exomes AF: 0.480 AC: 120288 AN: 250814 Hom.: 30245 AF XY: 0.488 AC XY: 66136 AN XY: 135660

Gnomad AFR exome AF: 0.503

Gnomad AMR exome AF: 0.489

Gnomad ASJ exome AF: 0.558

Gnomad EAS exome AF: 0.593

Gnomad SAS exome AF: 0.644

Gnomad FIN exome AF: 0.320

Gnomad NFE exome AF: 0.435

Gnomad OTH exome AF: 0.475

GnomAD4 exome AF: 0.462 AC: 672564 AN: 1457160 Hom.: 160014 Cov.: 35 AF XY: 0.468 AC XY: 339349 AN XY: 725166

Gnomad4 AFR exome AF: 0.502

Gnomad4 AMR exome AF: 0.492

Gnomad4 ASJ exome AF: 0.555

Gnomad4 EAS exome AF: 0.651

Gnomad4 SAS exome AF: 0.638

Gnomad4 FIN exome AF: 0.331

Gnomad4 NFE exome AF: 0.441

Gnomad4 OTH exome AF: 0.487

GnomAD4 genome AF: 0.469 AC: 71199 AN: 151866 Hom.: 16911 Cov.: 31 AF XY: 0.470 AC XY: 34854 AN XY: 74232

Gnomad4 AFR AF: 0.500

Gnomad4 AMR AF: 0.502

Gnomad4 ASJ AF: 0.550

Gnomad4 EAS AF: 0.603

Gnomad4 SAS AF: 0.635

Gnomad4 FIN AF: 0.321

Gnomad4 NFE AF: 0.439

Gnomad4 OTH AF: 0.486

Alfa AF: 0.467 Hom.: 3101

Bravo AF: 0.480

Asia WGS AF: 0.649 AC: 2259 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.5
DANN	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs915667; hg19: chr6-29798140; COSMIC: COSV64405874; COSMIC: COSV64405874;