rs17875395

Positions:

• chr6-29827445-G-A

Variant summary

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

The ENST00000443049.1(HCG4P8):​n.920C>T 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 0.0433 in 355,054 control chromosomes in the GnomAD database, including 505 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 0.052 (288 hom., cov: 32)
  • Exomes 𝑓: 0.037 (217 hom.)
• Consequence: HCG4P8 ENST00000443049.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.314

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0805 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-G	NM_001363567.2	c.7-391G>A		intron_variant			NP_001350496.1
HLA-G	NM_001384280.1	c.7-391G>A		intron_variant			NP_001371209.1
HLA-G	NM_002127.6	c.-112-288G>A		intron_variant			NP_002118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HCG4P8	ENST00000443049.1	n.920C>T		non_coding_transcript_exon_variant	1/1
HLA-G	ENST00000376828.6	c.7-391G>A		intron_variant				ENSP00000366024	A2
HLA-G	ENST00000428701.6	n.67-288G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0517 AC: 7859 AN: 152094 Hom.: 282 Cov.: 32

Gnomad AFR AF: 0.0821

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0838

Gnomad ASJ AF: 0.0772

Gnomad EAS AF: 0.00753

Gnomad SAS AF: 0.0286

Gnomad FIN AF: 0.0105

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0360

Gnomad OTH AF: 0.0695

GnomAD4 exome AF: 0.0370 AC: 7508 AN: 202842 Hom.: 217 Cov.: 0 AF XY: 0.0364 AC XY: 4088 AN XY: 112168

Gnomad4 AFR exome AF: 0.0795

Gnomad4 AMR exome AF: 0.0851

Gnomad4 ASJ exome AF: 0.0718

Gnomad4 EAS exome AF: 0.00327

Gnomad4 SAS exome AF: 0.0353

Gnomad4 FIN exome AF: 0.0139

Gnomad4 NFE exome AF: 0.0331

Gnomad4 OTH exome AF: 0.0407

GnomAD4 genome AF: 0.0518 AC: 7879 AN: 152212 Hom.: 288 Cov.: 32 AF XY: 0.0493 AC XY: 3673 AN XY: 74428

Gnomad4 AFR AF: 0.0821

Gnomad4 AMR AF: 0.0843

Gnomad4 ASJ AF: 0.0772

Gnomad4 EAS AF: 0.00755

Gnomad4 SAS AF: 0.0290

Gnomad4 FIN AF: 0.0105

Gnomad4 NFE AF: 0.0360

Gnomad4 OTH AF: 0.0688

Alfa AF: 0.0404 Hom.: 16

Bravo AF: 0.0601

Asia WGS AF: 0.0260 AC: 90 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.66
DANN	Benign	0.57

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: rs17875395; hg19: chr6-29795222;