rs17875397

Positions:

• chr6-29827789-C-T

Variant summary

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

The ENST00000443049.1(HCG4P8):​n.576G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0405 in 1,551,432 control chromosomes in the GnomAD database, including 1,742 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 0.058 (370 hom., cov: 32)
  • Exomes 𝑓: 0.039 (1372 hom.)
• Consequence: HCG4P8 ENST00000443049.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.857

Genes affected

HCG4P8 (HGNC:22927): (HLA complex group 4 pseudogene 8)

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-G	NM_001384290.1			upstream_gene_variant		ENST00000360323.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HCG4P8	ENST00000443049.1	n.576G>A		non_coding_transcript_exon_variant	1/1
HLA-G	ENST00000376828.6	c.7-47C>T		intron_variant				A2
HLA-G	ENST00000428701.6	n.123C>T		non_coding_transcript_exon_variant	2/5
HLA-G	ENST00000360323.11			upstream_gene_variant			NM_001384290.1	P2

Frequencies

GnomAD3 genomes AF: 0.0577 AC: 8770 AN: 152114 Hom.: 364 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0852

Gnomad ASJ AF: 0.0772

Gnomad EAS AF: 0.00752

Gnomad SAS AF: 0.0286

Gnomad FIN AF: 0.0104

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0360

Gnomad OTH AF: 0.0725

GnomAD3 exomes AF: 0.0455 AC: 11247 AN: 247148 Hom.: 386 AF XY: 0.0428 AC XY: 5762 AN XY: 134486

Gnomad AFR exome AF: 0.104

Gnomad AMR exome AF: 0.0936

Gnomad ASJ exome AF: 0.0757

Gnomad EAS exome AF: 0.00388

Gnomad SAS exome AF: 0.0376

Gnomad FIN exome AF: 0.0117

Gnomad NFE exome AF: 0.0353

Gnomad OTH exome AF: 0.0496

GnomAD4 exome AF: 0.0386 AC: 54079 AN: 1399200 Hom.: 1372 Cov.: 25 AF XY: 0.0383 AC XY: 26795 AN XY: 699932

Gnomad4 AFR exome AF: 0.106

Gnomad4 AMR exome AF: 0.0944

Gnomad4 ASJ exome AF: 0.0777

Gnomad4 EAS exome AF: 0.00710

Gnomad4 SAS exome AF: 0.0380

Gnomad4 FIN exome AF: 0.0126

Gnomad4 NFE exome AF: 0.0353

Gnomad4 OTH exome AF: 0.0439

GnomAD4 genome AF: 0.0577 AC: 8790 AN: 152232 Hom.: 370 Cov.: 32 AF XY: 0.0550 AC XY: 4096 AN XY: 74430

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.0857

Gnomad4 ASJ AF: 0.0772

Gnomad4 EAS AF: 0.00754

Gnomad4 SAS AF: 0.0291

Gnomad4 FIN AF: 0.0104

Gnomad4 NFE AF: 0.0360

Gnomad4 OTH AF: 0.0717

Alfa AF: 0.0513 Hom.: 46

Bravo AF: 0.0670

Asia WGS AF: 0.0270 AC: 92 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.3
DANN	Benign	0.91

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs17875397; hg19: chr6-29795566;