rs2076177

Variant names:

• chr6-29725336-C-T
• rs2076177
• NM_001098479.2:c.886+30C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 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 (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 rank	MANE	Protein	UniProt
HLA-F	NM_001098479.2	c.886+30C>T		intron_variant	Intron 4 of 6	ENST00000259951.12	NP_001091949.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-F	ENST00000259951.12	c.886+30C>T		intron_variant	Intron 4 of 6	6	NM_001098479.2	ENSP00000259951.6

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

GnomAD2 exomes AF: 0.177 AC: 44462 AN: 250768 AF XY: 0.180

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 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

African (AFR) AF: 0.260 AC: 8689 AN: 33442

American (AMR) AF: 0.194 AC: 8671 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.180 AC: 4687 AN: 26108

East Asian (EAS) AF: 0.264 AC: 10476 AN: 39688

South Asian (SAS) AF: 0.295 AC: 25417 AN: 86224

European-Finnish (FIN) AF: 0.110 AC: 5892 AN: 53414

Middle Eastern (MID) AF: 0.216 AC: 1245 AN: 5768

European-Non Finnish (NFE) AF: 0.118 AC: 130681 AN: 1111162

Other (OTH) AF: 0.154 AC: 9292 AN: 60354

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

African (AFR) AF: 0.259 AC: 10674 AN: 41258

American (AMR) AF: 0.190 AC: 2897 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 621 AN: 3464

East Asian (EAS) AF: 0.298 AC: 1529 AN: 5138

South Asian (SAS) AF: 0.299 AC: 1432 AN: 4794

European-Finnish (FIN) AF: 0.107 AC: 1128 AN: 10584

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.123 AC: 8334 AN: 67912

Other (OTH) AF: 0.178 AC: 375 AN: 2108

Alfa AF: 0.140 Hom.: 743

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
PhyloP100		-0.83
PromoterAI		-0.0074	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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