rs915668

Positions:

• chr6-29830682-C-G

Variant summary

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

The NM_001384290.1(HLA-G):​c.*29-86C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 152,036 control chromosomes in the GnomAD database, including 22,848 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 (22848 hom., cov: 32)
  • Exomes 𝑓: 0.55 (73258 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-G NM_001384290.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0160

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=-1.03).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-G	NM_001384290.1	c.*29-86C>G		intron_variant		ENST00000360323.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-G	ENST00000360323.11	c.*29-86C>G		intron_variant			NM_001384290.1	P2

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82500 AN: 151918 Hom.: 22814 Cov.: 32

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.620

Gnomad SAS AF: 0.694

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.685

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.571

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.549 AC: 256619 AN: 467484 Hom.: 73258 Cov.: 0 AF XY: 0.563 AC XY: 142644 AN XY: 253508

Gnomad4 AFR exome AF: 0.629

Gnomad4 AMR exome AF: 0.646

Gnomad4 ASJ exome AF: 0.678

Gnomad4 EAS exome AF: 0.654

Gnomad4 SAS exome AF: 0.726

Gnomad4 FIN exome AF: 0.365

Gnomad4 NFE exome AF: 0.501

Gnomad4 OTH exome AF: 0.554

GnomAD4 genome AF: 0.543 AC: 82584 AN: 152036 Hom.: 22848 Cov.: 32 AF XY: 0.541 AC XY: 40175 AN XY: 74328

Gnomad4 AFR AF: 0.614

Gnomad4 AMR AF: 0.600

Gnomad4 ASJ AF: 0.645

Gnomad4 EAS AF: 0.619

Gnomad4 SAS AF: 0.695

Gnomad4 FIN AF: 0.351

Gnomad4 NFE AF: 0.495

Gnomad4 OTH AF: 0.576

Alfa AF: 0.514 Hom.: 2506

Bravo AF: 0.563

Asia WGS AF: 0.712 AC: 2475 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	8.0
DANN	Benign	0.23

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: rs915668; hg19: chr6-29798459; COSMIC: COSV64405412; COSMIC: COSV64405412;