chr6-29734733-G-A

Variant names:

• chr6-29734733-G-A
• rs2523395
• ENST00000465459.2:c.404-3389G>A

Variant summary

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

The XM_017010813.2(HLA-F):​c.1159-3389G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 151,872 control chromosomes in the GnomAD database, including 11,998 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 (11998 hom., cov: 31)
• Consequence: HLA-F XM_017010813.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.855

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• 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 rank	MANE	Protein	UniProt
HLA-F	XM_017010813.2	c.1159-3389G>A		intron_variant	Intron 7 of 7		XP_016866302.1
HLA-F	XM_011514564.2	c.1004-3389G>A		intron_variant	Intron 5 of 6		XP_011512866.1
HLA-F	XM_047418720.1	c.1004-3389G>A		intron_variant	Intron 5 of 5		XP_047274676.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-F	ENST00000465459.2	c.404-3389G>A		intron_variant	Intron 3 of 4	6		ENSP00000486947.1
HLA-F-AS1	ENST00000399247.6	n.1235+3233C>T		intron_variant	Intron 4 of 5	6

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59846 AN: 151752 Hom.: 11979 Cov.: 31

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.498

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.338

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.397

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

GnomAD4 genome AF: 0.394 AC: 59902 AN: 151872 Hom.: 11998 Cov.: 31 AF XY: 0.394 AC XY: 29255 AN XY: 74210

Gnomad4 AFR AF: 0.308

Gnomad4 AMR AF: 0.415

Gnomad4 ASJ AF: 0.498

Gnomad4 EAS AF: 0.425

Gnomad4 SAS AF: 0.294

Gnomad4 FIN AF: 0.431

Gnomad4 NFE AF: 0.436

Gnomad4 OTH AF: 0.396

Alfa AF: 0.421 Hom.: 18434

Bravo AF: 0.392

Asia WGS AF: 0.327 AC: 1136 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.2
DANN	Benign	0.42

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2523395; hg19: chr6-29702510; COSMIC: COSV67852553;