rs17875396

Variant names:

• chr6-29827454-G-A
• rs17875396
• ENST00000443049.1:n.911C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-29827454-G-A
• chr6-29827454-G-C

Variant summary

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

The ENST00000443049.1(HCG4P8):​n.911C>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 0.0434 in 356,700 control chromosomes in the GnomAD database, including 510 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 (287 hom., cov: 32)
  • Exomes 𝑓: 0.037 (223 hom.)
• Consequence: HCG4P8 ENST00000443049.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.727
• Publications: 4 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0805 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.7-382G>A		intron	N/A	NP_001350496.1
	HLA-G	NM_001384280.1		c.7-382G>A		intron	N/A	NP_001371209.1
	HLA-G	NM_002127.6		c.-112-279G>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.911C>T		non_coding_transcript_exon	Exon 1 of 1
	HLA-G	ENST00000376828.6	TSL:6	c.7-382G>A		intron	N/A	ENSP00000366024.2
	HLA-G	ENST00000428701.6	TSL:6	n.67-279G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0517 AC: 7869 AN: 152122 Hom.: 281 Cov.: 32

Gnomad AFR AF: 0.0822

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: 0.0106

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0360

Gnomad OTH AF: 0.0695

GnomAD4 exome AF: 0.0371 AC: 7594 AN: 204460 Hom.: 223 Cov.: 0 AF XY: 0.0366 AC XY: 4132 AN XY: 113050

African (AFR) AF: 0.0803 AC: 417 AN: 5192

American (AMR) AF: 0.0851 AC: 848 AN: 9970

Ashkenazi Jewish (ASJ) AF: 0.0735 AC: 331 AN: 4506

East Asian (EAS) AF: 0.00322 AC: 26 AN: 8068

South Asian (SAS) AF: 0.0353 AC: 1435 AN: 40702

European-Finnish (FIN) AF: 0.0139 AC: 128 AN: 9222

Middle Eastern (MID) AF: 0.0949 AC: 163 AN: 1718

European-Non Finnish (NFE) AF: 0.0334 AC: 3844 AN: 115216

Other (OTH) AF: 0.0407 AC: 402 AN: 9866

GnomAD4 genome AF: 0.0518 AC: 7889 AN: 152240 Hom.: 287 Cov.: 32 AF XY: 0.0494 AC XY: 3680 AN XY: 74450

African (AFR) AF: 0.0823 AC: 3416 AN: 41530

American (AMR) AF: 0.0843 AC: 1290 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0772 AC: 268 AN: 3472

East Asian (EAS) AF: 0.00755 AC: 39 AN: 5168

South Asian (SAS) AF: 0.0290 AC: 140 AN: 4828

European-Finnish (FIN) AF: 0.0106 AC: 112 AN: 10616

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0360 AC: 2450 AN: 68014

Other (OTH) AF: 0.0688 AC: 145 AN: 2108

Alfa AF: 0.0409 Hom.: 16

Bravo AF: 0.0601

Asia WGS AF: 0.0260 AC: 90 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.2
DANN	Benign	0.76
PhyloP100		-0.73
PromoterAI		0.043	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: rs17875396; hg19: chr6-29795231;