6-29723242-G-T

Variant names:

• chr6-29723242-G-T
• rs1362126
• ENST00000427340.1:n.730C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000427340.1(ENSG00000225864):​n.730C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000467 in 428,430 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 30)
  • Exomes 𝑓: 0.0000047 (0 hom.)
• Consequence: ENSG00000225864 ENST00000427340.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.516
• Publications: 0 publications found

Genes affected

ENSG00000225864 (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]

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-F	NM_001098479.2	c.-222G>T		upstream_gene_variant		ENST00000259951.12	NP_001091949.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-F	ENST00000259951.12	c.-222G>T		upstream_gene_variant		6	NM_001098479.2	ENSP00000259951.6

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000467 AC: 2 AN: 428430 Hom.: 0 Cov.: 4 AF XY: 0.00000443 AC XY: 1 AN XY: 225968

African (AFR) AF: 0.00 AC: 0 AN: 10788

American (AMR) AF: 0.00 AC: 0 AN: 14814

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12874

East Asian (EAS) AF: 0.0000723 AC: 2 AN: 27676

South Asian (SAS) AF: 0.00 AC: 0 AN: 41910

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32034

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1914

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 261786

Other (OTH) AF: 0.00 AC: 0 AN: 24634

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.4
DANN	Benign	0.73
PhyloP100		0.52
PromoterAI		0.038	Neutral

Splicing

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

Other links and lift over

dbSNP: rs1362126; hg19: chr6-29691019;