chr6-29826724-T-C

Variant names:

• chr6-29826724-T-C
• rs3115630

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 0.948 in 152,338 control chromosomes in the GnomAD database, including 68,542 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 0.95 (68542 hom., cov: 33)
• Consequence: HCG4P8 intragenic
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.85
• Publications: 16 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.978 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HCG4P8		n.29826724T>C		intragenic_variant
HLA-G	NM_001384280.1	c.-37+177T>C		intron_variant	Intron 1 of 8		NP_001371209.1
HLA-G	NM_001363567.2	c.-315T>C		upstream_gene_variant			NP_001350496.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-F-AS1	ENST00000849927.1	n.26+1747A>G		intron_variant	Intron 1 of 3
HLA-F-AS1	ENST00000849935.1	n.230+996A>G		intron_variant	Intron 1 of 2
HLA-G	ENST00000376828.6	c.-315T>C		upstream_gene_variant		6		ENSP00000366024.2

Frequencies

GnomAD3 genomes AF: 0.948 AC: 144273 AN: 152220 Hom.: 68481 Cov.: 33

Gnomad AFR AF: 0.986

Gnomad AMI AF: 0.956

Gnomad AMR AF: 0.956

Gnomad ASJ AF: 0.981

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.989

Gnomad FIN AF: 0.941

Gnomad MID AF: 0.972

Gnomad NFE AF: 0.915

Gnomad OTH AF: 0.950

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

GnomAD4 genome AF: 0.948 AC: 144393 AN: 152338 Hom.: 68542 Cov.: 33 AF XY: 0.949 AC XY: 70728 AN XY: 74494

African (AFR) AF: 0.986 AC: 40978 AN: 41570

American (AMR) AF: 0.956 AC: 14627 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.981 AC: 3407 AN: 3472

East Asian (EAS) AF: 0.998 AC: 5185 AN: 5194

South Asian (SAS) AF: 0.989 AC: 4776 AN: 4830

European-Finnish (FIN) AF: 0.941 AC: 9993 AN: 10618

Middle Eastern (MID) AF: 0.969 AC: 285 AN: 294

European-Non Finnish (NFE) AF: 0.915 AC: 62259 AN: 68030

Other (OTH) AF: 0.950 AC: 2011 AN: 2116

Alfa AF: 0.931 Hom.: 163328

Bravo AF: 0.951

Asia WGS AF: 0.991 AC: 3446 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.5
DANN	Benign	0.25
PhyloP100		-1.9
PromoterAI		0.013	Neutral

Splicing

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

Other links and lift over

dbSNP: rs3115630; hg19: chr6-29794501;