Genetic Variant HLA-F:c.404-240A>G (chr6-29737882-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000465459.2(HLA-F):c.404-240A>G 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 152,062 control chromosomes in the GnomAD database, including 12,015 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 ( 12007 hom., cov: 31)

Exomes 𝑓: 0.53 ( 8 hom. )

Consequence

HLA-F
ENST00000465459.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.288

Publications

66 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:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript ENST00000465459.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.99).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000465459.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-F-AS1	NR_026972.1		n.1235+84T>C		intron	N/A
	HLA-F-AS1	NR_026973.1		n.151-10743T>C		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HLA-F	ENST00000465459.2	TSL:6	c.404-240A>G	intron	N/A	ENSP00000486947.1	A0A0D9SFW8
HLA-F-AS1	ENST00000434086.2	TSL:6	n.1128T>C	non_coding_transcript_exon	Exon 4 of 4
HLA-F-AS1	ENST00000849904.1		n.519T>C	non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.394

AC:

59885

AN:

151884

Hom.:

11988

Cov.:

show subpopulations

Gnomad AFR

AF:

0.308

Gnomad AMI

AF:

0.409

Gnomad AMR

AF:

0.415

Gnomad ASJ

AF:

0.500

Gnomad EAS

AF:

0.424

Gnomad SAS

AF:

0.291

Gnomad FIN

AF:

0.428

Gnomad MID

AF:

0.335

Gnomad NFE

AF:

0.436

Gnomad OTH

AF:

0.397

GnomAD4 exome

AF:

0.534

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.521

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.394

AC:

59941

AN:

152004

Hom.:

12007

Cov.:

AF XY:

0.394

AC XY:

29266

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.308

AC:

12782

AN:

41464

American (AMR)

AF:

0.415

AC:

6341

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

1735

AN:

3468

East Asian (EAS)

AF:

0.424

AC:

2184

AN:

5152

South Asian (SAS)

AF:

0.293

AC:

1415

AN:

4822

European-Finnish (FIN)

AF:

0.428

AC:

4525

AN:

10570

Middle Eastern (MID)

AF:

0.340

AC:

100

AN:

294

European-Non Finnish (NFE)

AF:

0.436

AC:

29655

AN:

67942

Other (OTH)

AF:

0.395

AC:

833

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1870

3740

5609

7479

9349

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

556

1112

1668

2224

2780

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.421

Hom.:

46279

Bravo

AF:

0.393

Asia WGS

AF:

0.327

AC:

1136

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

3.7

(source)

DANN

Benign

0.70

PhyloP100

-0.29

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over