Genetic Variant ENST00000458236.1:n.1557G>A (chr6-29736306-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 ENST00000458236.1(HLA-F-AS1):n.1557G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.837 in 399,080 control chromosomes in the GnomAD database, including 140,767 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 0.82 ( 51072 hom., cov: 32)

Exomes 𝑓: 0.85 ( 89695 hom. )

Consequence

HLA-F-AS1
ENST00000458236.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.607

Publications

6 publications found

Variant links:

Genes affected

HLA-F-AS1 (HGNC:26645): (HLA-F antisense RNA 1)

HLA-F-AS1 links:

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:

Genome browser will be placed here

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=-1.0).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.961 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
HLA-F-AS1	NR_026972.1 link	n.1235+1660G>A	intron_variant	Intron 4 of 5
HLA-F-AS1	NR_026973.1 link	n.151-9167G>A	intron_variant	Intron 1 of 1
HLA-F	XM_017010813.2 link	c.1159-1816C>T	intron_variant	Intron 7 of 7	XP_016866302.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
HLA-F-AS1	ENST00000458236.1 link	n.1557G>A	non_coding_transcript_exon_variant	Exon 6 of 6	6
HLA-F	ENST00000465459.2 link	c.404-1816C>T	intron_variant	Intron 3 of 4	6	ENSP00000486947.1	A0A0D9SFW8
HLA-F-AS1	ENST00000399247.6 link	n.1235+1660G>A	intron_variant	Intron 4 of 5	6

Frequencies

GnomAD3 genomes

AF:

0.817

AC:

124165

AN:

152040

Hom.:

51011

Cov.:

show subpopulations

Gnomad AFR

AF:

0.789

Gnomad AMI

AF:

0.846

Gnomad AMR

AF:

0.867

Gnomad ASJ

AF:

0.875

Gnomad EAS

AF:

0.983

Gnomad SAS

AF:

0.927

Gnomad FIN

AF:

0.690

Gnomad MID

AF:

0.844

Gnomad NFE

AF:

0.818

Gnomad OTH

AF:

0.822

GnomAD4 exome

AF:

0.850

AC:

209789

AN:

246920

Hom.:

89695

Cov.:

AF XY:

0.858

AC XY:

121343

AN XY:

141392

show subpopulations

African (AFR)

AF:

0.789

AC:

4797

AN:

6076

American (AMR)

AF:

0.902

AC:

13760

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.883

AC:

6243

AN:

7070

East Asian (EAS)

AF:

0.987

AC:

8597

AN:

8706

South Asian (SAS)

AF:

0.918

AC:

44537

AN:

48496

European-Finnish (FIN)

AF:

0.727

AC:

7447

AN:

10242

Middle Eastern (MID)

AF:

0.840

AC:

2085

AN:

2482

European-Non Finnish (NFE)

AF:

0.823

AC:

112491

AN:

136736

Other (OTH)

AF:

0.830

AC:

9832

AN:

11852

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1439

2878

4317

5756

7195

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.817

AC:

124286

AN:

152160

Hom.:

51072

Cov.:

AF XY:

0.815

AC XY:

60609

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.789

AC:

32732

AN:

41484

American (AMR)

AF:

0.867

AC:

13249

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.875

AC:

3035

AN:

3470

East Asian (EAS)

AF:

0.983

AC:

5106

AN:

5192

South Asian (SAS)

AF:

0.928

AC:

4484

AN:

4832

European-Finnish (FIN)

AF:

0.690

AC:

7286

AN:

10556

Middle Eastern (MID)

AF:

0.846

AC:

247

AN:

292

European-Non Finnish (NFE)

AF:

0.818

AC:

55630

AN:

68020

Other (OTH)

AF:

0.825

AC:

1745

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1163

2326

3488

4651

5814

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.832

Hom.:

33444

Bravo

AF:

0.828

Asia WGS

AF:

0.939

AC:

3267

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

4.3

(source)

DANN

Benign

0.35

PhyloP100

-0.61

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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ENST00000458236.1:n.1557G>A

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