rs17875389

Variant names:

• chr6-29826707-A-G
• rs17875389

Variant summary

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

The variant allele was found at a frequency of 0.0578 in 152,334 control chromosomes in the GnomAD database, including 370 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: 33)
• Consequence: HCG4P8 intragenic
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.515
• Publications: 9 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=-0.92).
• 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 rank	MANE	Protein	UniProt
HCG4P8		n.29826707A>G		intragenic_variant
HLA-G	NM_001384280.1	c.-37+160A>G		intron_variant	Intron 1 of 8		NP_001371209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-F-AS1	ENST00000849927.1	n.26+1764T>C		intron_variant	Intron 1 of 3
HLA-F-AS1	ENST00000849935.1	n.230+1013T>C		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.0577 AC: 8778 AN: 152216 Hom.: 364 Cov.: 33

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0852

Gnomad ASJ AF: 0.0767

Gnomad EAS AF: 0.00749

Gnomad SAS AF: 0.0285

Gnomad FIN AF: 0.0105

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0361

Gnomad OTH AF: 0.0721

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0578 AC: 8798 AN: 152334 Hom.: 370 Cov.: 33 AF XY: 0.0550 AC XY: 4100 AN XY: 74502

African (AFR) AF: 0.103 AC: 4293 AN: 41552

American (AMR) AF: 0.0858 AC: 1313 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0767 AC: 266 AN: 3468

East Asian (EAS) AF: 0.00751 AC: 39 AN: 5192

South Asian (SAS) AF: 0.0290 AC: 140 AN: 4834

European-Finnish (FIN) AF: 0.0105 AC: 112 AN: 10628

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

European-Non Finnish (NFE) AF: 0.0361 AC: 2455 AN: 68030

Other (OTH) AF: 0.0714 AC: 151 AN: 2116

Alfa AF: 0.0454 Hom.: 22

Bravo AF: 0.0669

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	-0.92
CADD	Benign	3.6
DANN	Benign	0.30
PhyloP100		-0.52
PromoterAI		-0.011	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17875389; hg19: chr6-29794484;