rs1736936

Variant names:

• chr6-29826540-G-A
• rs1736936

Your query was ambiguous. Multiple possible variants found:

• chr6-29826540-G-A
• chr6-29826540-G-C
• chr6-29826540-G-T

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 0.483 in 151,868 control chromosomes in the GnomAD database, including 17,930 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 0.48 (17930 hom., cov: 31)
• Consequence: HCG4P8 intragenic
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.702
• Publications: 42 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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HCG4P8		n.29826540G>A		intragenic_variant
HLA-G	NM_001384280.1	c.-44G>A		5_prime_UTR_variant	Exon 1 of 9		NP_001371209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-F-AS1	ENST00000849927.1	n.26+1931C>T		intron_variant	Intron 1 of 3
HLA-F-AS1	ENST00000849935.1	n.230+1180C>T		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.483 AC: 73252 AN: 151750 Hom.: 17914 Cov.: 31

Gnomad AFR AF: 0.507

Gnomad AMI AF: 0.461

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.567

Gnomad EAS AF: 0.609

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.496

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

GnomAD4 genome AF: 0.483 AC: 73306 AN: 151868 Hom.: 17930 Cov.: 31 AF XY: 0.482 AC XY: 35812 AN XY: 74222

African (AFR) AF: 0.507 AC: 20992 AN: 41388

American (AMR) AF: 0.508 AC: 7752 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.567 AC: 1968 AN: 3470

East Asian (EAS) AF: 0.608 AC: 3126 AN: 5140

South Asian (SAS) AF: 0.665 AC: 3198 AN: 4808

European-Finnish (FIN) AF: 0.340 AC: 3586 AN: 10552

Middle Eastern (MID) AF: 0.568 AC: 166 AN: 292

European-Non Finnish (NFE) AF: 0.457 AC: 31045 AN: 67950

Other (OTH) AF: 0.502 AC: 1055 AN: 2102

Alfa AF: 0.479 Hom.: 64165

Bravo AF: 0.493

Asia WGS AF: 0.678 AC: 2360 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.52
DANN	Benign	0.40
PhyloP100		-0.70
PromoterAI		-0.0044	Neutral

Splicing

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

Other links and lift over

dbSNP: rs1736936; hg19: chr6-29794317; COSMIC: COSV64407025;