rs2735059

Variant names:

• chr6-29728077-G-A
• rs2735059
• XM_017010810.1:c.1279G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-29728077-G-A
• chr6-29728077-G-C

Variant summary

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

The XM_017010810.1(HLA-F):​c.1279G>A​(p.Glu427Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 518,512 control chromosomes in the GnomAD database, including 47,342 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/5 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.42 (13781 hom., cov: 32)
  • Exomes 𝑓: 0.42 (33561 hom.)
• Consequence: HLA-F XM_017010810.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.452
• Publications: 30 publications found

Genes affected

HLA-F (HGNC:4963): (major histocompatibility complex, class I, F) This gene belongs to the HLA class I heavy chain paralogues. It encodes a non-classical heavy chain that forms a heterodimer with a beta-2 microglobulin light chain, with the heavy chain anchored in the membrane. Unlike most other HLA heavy chains, this molecule is localized in the endoplasmic reticulum and Golgi apparatus, with a small amount present at the cell surface in some cell types. It contains a divergent peptide-binding groove, and is thought to bind a restricted subset of peptides for immune presentation. This gene exhibits few polymorphisms. Multiple transcript variants encoding different isoforms have been found for this gene. These variants lack a coding exon found in transcripts from other HLA paralogues due to an altered splice acceptor site, resulting in a shorter cytoplasmic domain. [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 (REVEL=0.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000475996.1. 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-F-AS1	NR_026972.1		n.1366+288C>T		intron	N/A
	HLA-F-AS1	NR_026973.1		n.151-938C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-F	ENST00000475996.1	TSL:6	c.*14G>A		3_prime_UTR	Exon 2 of 2	ENSP00000486309.1
	HLA-F	ENST00000465459.2	TSL:6	c.403+2034G>A		intron	N/A	ENSP00000486947.1
	HLA-F-AS1	ENST00000399247.6	TSL:6	n.1366+288C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64489 AN: 152000 Hom.: 13765 Cov.: 32

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.426

Gnomad ASJ AF: 0.521

Gnomad EAS AF: 0.416

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.434

GnomAD2 exomes AF: 0.422 AC: 96443 AN: 228538 AF XY: 0.418

Gnomad AFR exome AF: 0.385

Gnomad AMR exome AF: 0.420

Gnomad ASJ exome AF: 0.520

Gnomad EAS exome AF: 0.421

Gnomad FIN exome AF: 0.440

Gnomad NFE exome AF: 0.459

Gnomad OTH exome AF: 0.431

GnomAD4 exome AF: 0.420 AC: 153810 AN: 366396 Hom.: 33561 Cov.: 0 AF XY: 0.411 AC XY: 86301 AN XY: 210090

African (AFR) AF: 0.378 AC: 3972 AN: 10508

American (AMR) AF: 0.419 AC: 15160 AN: 36222

Ashkenazi Jewish (ASJ) AF: 0.517 AC: 6067 AN: 11740

East Asian (EAS) AF: 0.417 AC: 5495 AN: 13166

South Asian (SAS) AF: 0.284 AC: 18959 AN: 66742

European-Finnish (FIN) AF: 0.449 AC: 7592 AN: 16896

Middle Eastern (MID) AF: 0.433 AC: 1232 AN: 2842

European-Non Finnish (NFE) AF: 0.460 AC: 88116 AN: 191678

Other (OTH) AF: 0.435 AC: 7217 AN: 16602

GnomAD4 genome AF: 0.424 AC: 64539 AN: 152116 Hom.: 13781 Cov.: 32 AF XY: 0.423 AC XY: 31433 AN XY: 74348

African (AFR) AF: 0.389 AC: 16160 AN: 41496

American (AMR) AF: 0.426 AC: 6512 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.521 AC: 1807 AN: 3470

East Asian (EAS) AF: 0.416 AC: 2150 AN: 5172

South Asian (SAS) AF: 0.293 AC: 1410 AN: 4818

European-Finnish (FIN) AF: 0.435 AC: 4609 AN: 10588

Middle Eastern (MID) AF: 0.438 AC: 128 AN: 292

European-Non Finnish (NFE) AF: 0.448 AC: 30474 AN: 67972

Other (OTH) AF: 0.432 AC: 912 AN: 2112

Alfa AF: 0.446 Hom.: 21334

Bravo AF: 0.425

Asia WGS AF: 0.327 AC: 1134 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.2
DANN	Benign	0.77
PhyloP100		0.45
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2735059; hg19: chr6-29695854; COSMIC: COSV52575182;