rs2523399

Positions:

• chr6-29732302-C-T

Variant summary

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

The XM_047418718.1(HLA-F):​c.1159-889C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 151,892 control chromosomes in the GnomAD database, including 24,016 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 0.56 (24016 hom., cov: 31)
• Consequence: HLA-F XM_047418718.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.627

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-F	XM_047418718.1	c.1159-889C>T		intron_variant			XP_047274674.1
HLA-F	XM_047418719.1	c.1126-889C>T		intron_variant			XP_047274675.1
HLA-F	XM_017010813.2	c.1158+5298C>T		intron_variant			XP_016866302.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-F	ENST00000465459.2	c.404-5820C>T		intron_variant		6		ENSP00000486947.1
HLA-F-AS1	ENST00000399247.6	n.1236-3807G>A		intron_variant		6

Frequencies

GnomAD3 genomes AF: 0.560 AC: 84958 AN: 151774 Hom.: 23978 Cov.: 31

Gnomad AFR AF: 0.533

Gnomad AMI AF: 0.577

Gnomad AMR AF: 0.586

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.723

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.555

Gnomad OTH AF: 0.558

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.560 AC: 85047 AN: 151892 Hom.: 24016 Cov.: 31 AF XY: 0.563 AC XY: 41795 AN XY: 74232

Gnomad4 AFR AF: 0.534

Gnomad4 AMR AF: 0.585

Gnomad4 ASJ AF: 0.642

Gnomad4 EAS AF: 0.723

Gnomad4 SAS AF: 0.592

Gnomad4 FIN AF: 0.537

Gnomad4 NFE AF: 0.555

Gnomad4 OTH AF: 0.555

Alfa AF: 0.560 Hom.: 25349

Bravo AF: 0.563

Asia WGS AF: 0.548 AC: 1902 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.18
DANN	Benign	0.19

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2523399; hg19: chr6-29700079;