Variant 6-29724080-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001098479.2(HLA-F):c.335-93C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 1,562,232 control chromosomes in the GnomAD database, including 146,011 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 0.42 ( 13781 hom., cov: 32)

Exomes 𝑓: 0.43 ( 132230 hom. )

Consequence

HLA-F
NM_001098479.2 intron

Scores

Splicing: ADA: 0.00006217

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.75

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 (HGNC:):

HLA-F 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=-1.02).

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	MANE	Protein	UniProt
HLA-F	NM_001098479.2 linkuse as main transcript	c.335-93C>G		intron_variant		ENST00000259951.12	NP_001091949.1	P30511-3Q5JZ48

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-F	ENST00000259951.12 linkuse as main transcript	c.335-93C>G		intron_variant		6	NM_001098479.2	ENSP00000259951.6		P30511-3

Frequencies

GnomAD3 genomes

AF:

0.424

AC:

64449

AN:

151882

Hom.:

13765

Cov.:

show subpopulations

Gnomad AFR

AF:

0.389

Gnomad AMI

AF:

0.420

Gnomad AMR

AF:

0.426

Gnomad ASJ

AF:

0.520

Gnomad EAS

AF:

0.416

Gnomad SAS

AF:

0.291

Gnomad FIN

AF:

0.435

Gnomad MID

AF:

0.430

Gnomad NFE

AF:

0.448

Gnomad OTH

AF:

0.435

GnomAD3 exomes

AF:

0.421

AC:

71565

AN:

169952

Hom.:

15512

AF XY:

0.415

AC XY:

38524

AN XY:

92934

show subpopulations

Gnomad AFR exome

AF:

0.382

Gnomad AMR exome

AF:

0.420

Gnomad ASJ exome

AF:

0.523

Gnomad EAS exome

AF:

0.426

Gnomad SAS exome

AF:

0.277

Gnomad FIN exome

AF:

0.446

Gnomad NFE exome

AF:

0.458

Gnomad OTH exome

AF:

0.427

GnomAD4 exome

AF:

0.430

AC:

606294

AN:

1410230

Hom.:

132230

Cov.:

AF XY:

0.426

AC XY:

297476

AN XY:

697490

show subpopulations

Gnomad4 AFR exome

AF:

0.378

Gnomad4 AMR exome

AF:

0.414

Gnomad4 ASJ exome

AF:

0.519

Gnomad4 EAS exome

AF:

0.411

Gnomad4 SAS exome

AF:

0.283

Gnomad4 FIN exome

AF:

0.445

Gnomad4 NFE exome

AF:

0.441

Gnomad4 OTH exome

AF:

0.425

GnomAD4 genome

AF:

0.424

AC:

64498

AN:

152002

Hom.:

13781

Cov.:

AF XY:

0.423

AC XY:

31407

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.390

Gnomad4 AMR

AF:

0.426

Gnomad4 ASJ

AF:

0.520

Gnomad4 EAS

AF:

0.415

Gnomad4 SAS

AF:

0.294

Gnomad4 FIN

AF:

0.435

Gnomad4 NFE

AF:

0.448

Gnomad4 OTH

AF:

0.433

Alfa

AF:

0.419

Hom.:

4113

Bravo

AF:

0.425

Asia WGS

AF:

0.328

AC:

1138

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

1.7

DANN

Benign

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000062

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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