rs2394160

Positions:

• chr6-29735485-A-G
• chr6-29735485-A-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.151-8346T>C 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 0.394 in 150,468 control chromosomes in the GnomAD database, including 11,851 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 0.39 (11851 hom., cov: 28)
  • Failed GnomAD Quality Control
• Consequence: HLA-F-AS1 NR_026973.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.211

Genes affected

HLA-F-AS1 (HGNC:26645): (HLA-F antisense RNA 1)

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-F-AS1	NR_026973.1	n.151-8346T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-F	ENST00000465459.2	c.404-2637A>G		intron_variant				ENSP00000486947
HLA-F-AS1	ENST00000458236.1	n.2378T>C		non_coding_transcript_exon_variant	6/6

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59189 AN: 150366 Hom.: 11835 Cov.: 28

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.410

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.500

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.338

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.397

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.394 AC: 59235 AN: 150468 Hom.: 11851 Cov.: 28 AF XY: 0.393 AC XY: 28867 AN XY: 73422

Gnomad4 AFR AF: 0.307

Gnomad4 AMR AF: 0.415

Gnomad4 ASJ AF: 0.500

Gnomad4 EAS AF: 0.425

Gnomad4 SAS AF: 0.292

Gnomad4 FIN AF: 0.425

Gnomad4 NFE AF: 0.436

Gnomad4 OTH AF: 0.395

Alfa AF: 0.424 Hom.: 13301

Bravo AF: 0.392

Asia WGS AF: 0.325 AC: 1126 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.4
DANN	Benign	0.61

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2394160; hg19: chr6-29703262;