Variant rs2735059 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The XM_017010810.1(HLA-F):c.1279G>A(p.Glu427Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 518,512 control chromosomes in the GnomAD database, including 47,342 homozygotes. In-silico tool predicts a benign outcome for this variant. 4/4 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.42 ( 13781 hom., cov: 32)

Exomes 𝑓: 0.42 ( 33561 hom. )

Consequence

HLA-F
XM_017010810.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.452

Variant links:

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 links:

HLA-F-AS1 (HGNC:):

HLA-F-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	Protein
HLA-F	XM_017010810.1 linkuse as main transcript	c.1279G>A	p.Glu427Lys	missense_variant	8/8	XP_016866299.1
HLA-F	XM_047418718.1 linkuse as main transcript	c.1158+1073G>A		intron_variant		XP_047274674.1
HLA-F	XM_047418719.1 linkuse as main transcript	c.1125+1073G>A		intron_variant		XP_047274675.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	Protein	UniProt
HLA-F	ENST00000475996.1 linkuse as main transcript	c.*14G>A	3_prime_UTR_variant	2/2	6	ENSP00000486309.1	A0A0D9SF55
HLA-F	ENST00000465459.2 linkuse as main transcript	c.403+2034G>A	intron_variant		6	ENSP00000486947.1	A0A0D9SFW8
HLA-F-AS1	ENST00000399247.6 linkuse as main transcript	n.1366+288C>T	intron_variant		6

Frequencies

GnomAD3 genomes

AF:

0.424

AC:

64489

AN:

152000

Hom.:

13765

Cov.:

show subpopulations

Gnomad AFR

AF:

0.389

Gnomad AMI

AF:

0.417

Gnomad AMR

AF:

0.426

Gnomad ASJ

AF:

0.521

Gnomad EAS

AF:

0.416

Gnomad SAS

AF:

0.290

Gnomad FIN

AF:

0.435

Gnomad MID

AF:

0.433

Gnomad NFE

AF:

0.448

Gnomad OTH

AF:

0.434

GnomAD3 exomes

AF:

0.422

AC:

96443

AN:

228538

Hom.:

20861

AF XY:

0.418

AC XY:

52770

AN XY:

126338

show subpopulations

Gnomad AFR exome

AF:

0.385

Gnomad AMR exome

AF:

0.420

Gnomad ASJ exome

AF:

0.520

Gnomad EAS exome

AF:

0.421

Gnomad SAS exome

AF:

0.272

Gnomad FIN exome

AF:

0.440

Gnomad NFE exome

AF:

0.459

Gnomad OTH exome

AF:

0.431

GnomAD4 exome

AF:

0.420

AC:

153810

AN:

366396

Hom.:

33561

Cov.:

AF XY:

0.411

AC XY:

86301

AN XY:

210090

show subpopulations

Gnomad4 AFR exome

AF:

0.378

Gnomad4 AMR exome

AF:

0.419

Gnomad4 ASJ exome

AF:

0.517

Gnomad4 EAS exome

AF:

0.417

Gnomad4 SAS exome

AF:

0.284

Gnomad4 FIN exome

AF:

0.449

Gnomad4 NFE exome

AF:

0.460

Gnomad4 OTH exome

AF:

0.435

GnomAD4 genome

AF:

0.424

AC:

64539

AN:

152116

Hom.:

13781

Cov.:

AF XY:

0.423

AC XY:

31433

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.389

Gnomad4 AMR

AF:

0.426

Gnomad4 ASJ

AF:

0.521

Gnomad4 EAS

AF:

0.416

Gnomad4 SAS

AF:

0.293

Gnomad4 FIN

AF:

0.435

Gnomad4 NFE

AF:

0.448

Gnomad4 OTH

AF:

0.432

Alfa

AF:

0.459

Hom.:

13562

Bravo

AF:

0.425

Asia WGS

AF:

0.327

AC:

1134

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

7.2

DANN

Benign

0.77

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over