6-29732302-C-T

Variant names:

• chr6-29732302-C-T
• rs2523399
• ENST00000465459.2:c.404-5820C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000465459.2(HLA-F):​c.404-5820C>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 ENST00000465459.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.627
• Publications: 31 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000465459.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-F-AS1	NR_026972.1		n.1236-3807G>A		intron	N/A
	HLA-F-AS1	NR_026973.1		n.151-5163G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-F	ENST00000465459.2	TSL:6	c.404-5820C>T		intron	N/A	ENSP00000486947.1	A0A0D9SFW8
	HLA-F-AS1	ENST00000399247.6	TSL:6	n.1236-3807G>A		intron	N/A
	HLA-F-AS1	ENST00000849873.1		n.422-5163G>A		intron	N/A

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

African (AFR) AF: 0.534 AC: 22084 AN: 41380

American (AMR) AF: 0.585 AC: 8935 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.642 AC: 2226 AN: 3466

East Asian (EAS) AF: 0.723 AC: 3742 AN: 5174

South Asian (SAS) AF: 0.592 AC: 2845 AN: 4808

European-Finnish (FIN) AF: 0.537 AC: 5669 AN: 10556

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.555 AC: 37703 AN: 67926

Other (OTH) AF: 0.555 AC: 1170 AN: 2110

Alfa AF: 0.554 Hom.: 75336

Bravo AF: 0.563

Asia WGS AF: 0.548 AC: 1902 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.18
DANN	Benign	0.19
PhyloP100		-0.63
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2523399;

hg19: chr6-29700079;