rs885945

chr6-29729075-C-T

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.151-1936G>A 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 0.2 in 152,074 control chromosomes in the GnomAD database, including 3,257 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 0.20 (3256 hom., cov: 32)
  • Exomes 𝑓: 1.0 (1 hom.)
• Consequence: HLA-F-AS1 NR_026973.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.680

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-F-AS1	NR_026973.1	n.151-1936G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-F	ENST00000475996.1	c.*1012C>T		3_prime_UTR_variant	2/2
HLA-F	ENST00000465459.2	c.403+3032C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30370 AN: 151954 Hom.: 3247 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.195

GnomAD4 exome AF: 1.00 AC: 2 AN: 2 Hom.: 1 Cov.: 0 AF XY: 1.00 AC XY: 2 AN XY: 2

Gnomad4 FIN exome AF: 1.00

GnomAD4 genome AF: 0.200 AC: 30393 AN: 152072 Hom.: 3256 Cov.: 32 AF XY: 0.198 AC XY: 14688 AN XY: 74316

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.223

Gnomad4 ASJ AF: 0.174

Gnomad4 EAS AF: 0.262

Gnomad4 SAS AF: 0.321

Gnomad4 FIN AF: 0.134

Gnomad4 NFE AF: 0.226

Gnomad4 OTH AF: 0.202

Alfa AF: 0.227 Hom.: 950

Bravo AF: 0.201

Asia WGS AF: 0.379 AC: 1321 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	2.9
Dann	Benign	0.28

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs885945; hg19: chr6-29696852;