rs2076177

Positions:

• chr6-29725336-C-T

Variant summary

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

The NM_001098479.2(HLA-F):​c.886+30C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 1,612,550 control chromosomes in the GnomAD database, including 19,689 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 0.18 (2846 hom., cov: 32)
  • Exomes 𝑓: 0.14 (16843 hom.)
• Consequence: HLA-F NM_001098479.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.835

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]

ACMG classification

Verdict is Benign. Variant got -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 = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-F	NM_001098479.2	c.886+30C>T		intron_variant		ENST00000259951.12	NP_001091949.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-F	ENST00000259951.12	c.886+30C>T		intron_variant			NM_001098479.2	ENSP00000259951	A2

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27157 AN: 151584 Hom.: 2838 Cov.: 32

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.180

GnomAD3 exomes AF: 0.177 AC: 44462 AN: 250768 Hom.: 4814 AF XY: 0.180 AC XY: 24347 AN XY: 135588

Gnomad AFR exome AF: 0.260

Gnomad AMR exome AF: 0.195

Gnomad ASJ exome AF: 0.175

Gnomad EAS exome AF: 0.321

Gnomad SAS exome AF: 0.288

Gnomad FIN exome AF: 0.109

Gnomad NFE exome AF: 0.121

Gnomad OTH exome AF: 0.161

GnomAD4 exome AF: 0.140 AC: 205050 AN: 1460850 Hom.: 16843 Cov.: 35 AF XY: 0.145 AC XY: 105445 AN XY: 726780

Gnomad4 AFR exome AF: 0.260

Gnomad4 AMR exome AF: 0.194

Gnomad4 ASJ exome AF: 0.180

Gnomad4 EAS exome AF: 0.264

Gnomad4 SAS exome AF: 0.295

Gnomad4 FIN exome AF: 0.110

Gnomad4 NFE exome AF: 0.118

Gnomad4 OTH exome AF: 0.154

GnomAD4 genome AF: 0.179 AC: 27192 AN: 151700 Hom.: 2846 Cov.: 32 AF XY: 0.182 AC XY: 13459 AN XY: 74140

Gnomad4 AFR AF: 0.259

Gnomad4 AMR AF: 0.190

Gnomad4 ASJ AF: 0.179

Gnomad4 EAS AF: 0.298

Gnomad4 SAS AF: 0.299

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.178

Alfa AF: 0.142 Hom.: 494

Bravo AF: 0.186

Asia WGS AF: 0.222 AC: 771 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	6.4
DANN	Benign	0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2076177; hg19: chr6-29693113; COSMIC: COSV52574587; COSMIC: COSV52574587;