rs1736934

Variant names:

• chr6-29826705-A-T
• rs1736934

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 0.34 in 152,162 control chromosomes in the GnomAD database, including 8,945 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 0.34 (8945 hom., cov: 33)
• Consequence: HCG4P8 intragenic
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.915
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.446 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HCG4P8		n.29826705A>T		intragenic_variant
HLA-G	NM_001384280.1	c.-37+158A>T		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+1766T>A		intron_variant	Intron 1 of 3
HLA-F-AS1	ENST00000849935.1	n.230+1015T>A		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51618 AN: 152042 Hom.: 8934 Cov.: 33

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.458

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.373

Gnomad OTH AF: 0.346

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

GnomAD4 genome AF: 0.340 AC: 51662 AN: 152162 Hom.: 8945 Cov.: 33 AF XY: 0.337 AC XY: 25081 AN XY: 74396

African (AFR) AF: 0.286 AC: 11883 AN: 41488

American (AMR) AF: 0.340 AC: 5196 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.458 AC: 1588 AN: 3470

East Asian (EAS) AF: 0.306 AC: 1584 AN: 5180

South Asian (SAS) AF: 0.462 AC: 2229 AN: 4822

European-Finnish (FIN) AF: 0.252 AC: 2666 AN: 10596

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.373 AC: 25331 AN: 67992

Other (OTH) AF: 0.346 AC: 731 AN: 2112

Alfa AF: 0.357 Hom.: 1192

Bravo AF: 0.341

Asia WGS AF: 0.355 AC: 1239 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	6.8
DANN	Benign	0.27
PhyloP100		0.92
PromoterAI		-0.0022	Neutral

Splicing

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

Other links and lift over

dbSNP: rs1736934; hg19: chr6-29794482;