rs17875394

Variant names:

• chr6-29827402-G-A
• rs17875394
• ENST00000443049.1:n.963C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000443049.1(HCG4P8):​n.963C>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 0.00869 in 354,404 control chromosomes in the GnomAD database, including 118 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 0.0097 (61 hom., cov: 32)
  • Exomes 𝑓: 0.0079 (57 hom.)
• Consequence: HCG4P8 ENST00000443049.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.29
• Publications: 5 publications found

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]

HLA-F-AS1 (HGNC:26645): (HLA-F antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0849 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000443049.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-G	NM_001363567.2		c.6+358G>A		intron	N/A	NP_001350496.1
	HLA-G	NM_001384280.1		c.6+358G>A		intron	N/A	NP_001371209.1
	HLA-G	NM_002127.6		c.-112-331G>A		intron	N/A	NP_002118.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HCG4P8	ENST00000443049.1	TSL:6	n.963C>T		non_coding_transcript_exon	Exon 1 of 1
	HLA-G	ENST00000376828.6	TSL:6	c.6+358G>A		intron	N/A	ENSP00000366024.2
	HLA-G	ENST00000428701.6	TSL:6	n.67-331G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00962 AC: 1463 AN: 152158 Hom.: 60 Cov.: 32

Gnomad AFR AF: 0.00147

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0541

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.0915

Gnomad SAS AF: 0.00331

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000779

Gnomad OTH AF: 0.00955

GnomAD4 exome AF: 0.00794 AC: 1605 AN: 202128 Hom.: 57 Cov.: 0 AF XY: 0.00745 AC XY: 832 AN XY: 111680

African (AFR) AF: 0.00174 AC: 9 AN: 5176

American (AMR) AF: 0.0663 AC: 668 AN: 10070

Ashkenazi Jewish (ASJ) AF: 0.00137 AC: 6 AN: 4388

East Asian (EAS) AF: 0.0863 AC: 693 AN: 8032

South Asian (SAS) AF: 0.00201 AC: 81 AN: 40306

European-Finnish (FIN) AF: 0.00231 AC: 21 AN: 9110

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2150

European-Non Finnish (NFE) AF: 0.000628 AC: 71 AN: 113132

Other (OTH) AF: 0.00574 AC: 56 AN: 9764

GnomAD4 genome AF: 0.00967 AC: 1473 AN: 152276 Hom.: 61 Cov.: 32 AF XY: 0.0111 AC XY: 830 AN XY: 74470

African (AFR) AF: 0.00147 AC: 61 AN: 41548

American (AMR) AF: 0.0546 AC: 836 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3468

East Asian (EAS) AF: 0.0917 AC: 474 AN: 5170

South Asian (SAS) AF: 0.00332 AC: 16 AN: 4824

European-Finnish (FIN) AF: 0.00104 AC: 11 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000779 AC: 53 AN: 68024

Other (OTH) AF: 0.00992 AC: 21 AN: 2116

Alfa AF: 0.00689 Hom.: 17

Bravo AF: 0.0130

Asia WGS AF: 0.0430 AC: 149 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.5
DANN	Benign	0.80
PhyloP100		-2.3
PromoterAI		0.0069	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17875394; hg19: chr6-29795179;