dbSNP rs885945: HLA-F:c.*1012C>T (chr6-29729075-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000475996.1(HLA-F):c.*1012C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,074 control chromosomes in the GnomAD database, including 3,257 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 0.20 ( 3256 hom., cov: 32)

Exomes 𝑓: 1.0 ( 1 hom. )

Consequence

HLA-F
ENST00000475996.1 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.680

Publications

18 publications found

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:26645): (HLA-F antisense RNA 1)

HLA-F-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
HLA-F	XM_017010810.1 link	c.*969C>T	3_prime_UTR_variant	Exon 8 of 8	XP_016866299.1
HLA-F-AS1	NR_026972.1 link	n.1236-580G>A	intron_variant	Intron 4 of 5
HLA-F-AS1	NR_026973.1 link	n.151-1936G>A	intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
HLA-F	ENST00000475996.1 link	c.*1012C>T	3_prime_UTR_variant	Exon 2 of 2	6	ENSP00000486309.1	A0A0D9SF55
HLA-F	ENST00000465459.2 link	c.403+3032C>T	intron_variant	Intron 3 of 4	6	ENSP00000486947.1	A0A0D9SFW8
HLA-F-AS1	ENST00000399247.6 link	n.1236-580G>A	intron_variant	Intron 4 of 5	6

Frequencies

GnomAD3 genomes

AF:

0.200

AC:

30370

AN:

151954

Hom.:

3247

Cov.:

show subpopulations

Gnomad AFR

AF:

0.144

Gnomad AMI

AF:

0.257

Gnomad AMR

AF:

0.222

Gnomad ASJ

AF:

0.174

Gnomad EAS

AF:

0.262

Gnomad SAS

AF:

0.324

Gnomad FIN

AF:

0.134

Gnomad MID

AF:

0.222

Gnomad NFE

AF:

0.226

Gnomad OTH

AF:

0.195

GnomAD4 exome

AF:

1.00

AC:

AN:

Hom.:

Cov.:

AF XY:

1.00

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.200

AC:

30393

AN:

152072

Hom.:

3256

Cov.:

AF XY:

0.198

AC XY:

14688

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.144

AC:

5984

AN:

41470

American (AMR)

AF:

0.223

AC:

3406

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.174

AC:

603

AN:

3464

East Asian (EAS)

AF:

0.262

AC:

1354

AN:

5168

South Asian (SAS)

AF:

0.321

AC:

1547

AN:

4818

European-Finnish (FIN)

AF:

0.134

AC:

1416

AN:

10560

Middle Eastern (MID)

AF:

0.221

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.226

AC:

15357

AN:

67988

Other (OTH)

AF:

0.202

AC:

427

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1192

2384

3576

4768

5960

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.227

Hom.:

1156

Bravo

AF:

0.201

Asia WGS

AF:

0.379

AC:

1321

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.9

(source)

DANN

Benign

0.28

PhyloP100

0.68

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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rs885945

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over