rs2735059

chr6-29728077-G-Achr6-29728077-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_026973.1(HLA-F-AS1):n.151-938C>T variant causes a intron, non coding transcript 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. 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-AS1 NR_026973.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.452

Genes affected

HLA-F-AS1 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-F-AS1	NR_026973.1	n.151-938C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-F	ENST00000475996.1	c.*14G>A		3_prime_UTR_variant	2/2
HLA-F	ENST00000465459.2	c.403+2034G>A		intron_variant

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

GnomAD3 exomes AF: 0.422 AC: 96443 AN: 228538 Hom.: 20861 AF XY: 0.418 AC XY: 52770 AN XY: 126338

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 SAS exome AF: 0.272

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

Gnomad4 AFR exome AF: 0.378

Gnomad4 AMR exome AF: 0.419

Gnomad4 ASJ exome AF: 0.517

Gnomad4 EAS exome AF: 0.417

Gnomad4 SAS exome AF: 0.284

Gnomad4 FIN exome AF: 0.449

Gnomad4 NFE exome AF: 0.460

Gnomad4 OTH exome AF: 0.435

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

Gnomad4 AFR AF: 0.389

Gnomad4 AMR AF: 0.426

Gnomad4 ASJ AF: 0.521

Gnomad4 EAS AF: 0.416

Gnomad4 SAS AF: 0.293

Gnomad4 FIN AF: 0.435

Gnomad4 NFE AF: 0.448

Gnomad4 OTH AF: 0.432

Alfa AF: 0.459 Hom.: 13562

Bravo AF: 0.425

Asia WGS AF: 0.327 AC: 1134 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	7.2
Dann	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

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