dbSNP rs1362126: ENSG00000225864:n.730C>T (chr6-29723242-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000427340.1(ENSG00000225864):n.730C>T 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 0.374 in 579,436 control chromosomes in the GnomAD database, including 42,614 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 0.35 ( 9767 hom., cov: 30)

Exomes 𝑓: 0.38 ( 32847 hom. )

Consequence

ENSG00000225864
ENST00000427340.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.516

Publications

57 publications found

Variant links:

Genes affected

ENSG00000225864 (HGNC:):

ENSG00000225864 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:

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

HLA-F-AS1 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=-0.87).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-F	NM_001098479.2 link	c.-222G>A		upstream_gene_variant		ENST00000259951.12	NP_001091949.1	P30511-3Q5JZ48

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-F	ENST00000259951.12 link	c.-222G>A		upstream_gene_variant		6	NM_001098479.2	ENSP00000259951.6		P30511-3

Frequencies

GnomAD3 genomes

AF:

0.350

AC:

53071

AN:

151836

Hom.:

9762

Cov.:

show subpopulations

Gnomad AFR

AF:

0.229

Gnomad AMI

AF:

0.417

Gnomad AMR

AF:

0.363

Gnomad ASJ

AF:

0.463

Gnomad EAS

AF:

0.406

Gnomad SAS

AF:

0.210

Gnomad FIN

AF:

0.424

Gnomad MID

AF:

0.280

Gnomad NFE

AF:

0.408

Gnomad OTH

AF:

0.351

GnomAD4 exome

AF:

0.382

AC:

163378

AN:

427480

Hom.:

32847

Cov.:

AF XY:

0.373

AC XY:

84088

AN XY:

225490

show subpopulations

African (AFR)

AF:

0.215

AC:

2313

AN:

10770

American (AMR)

AF:

0.344

AC:

5088

AN:

14774

Ashkenazi Jewish (ASJ)

AF:

0.458

AC:

5882

AN:

12856

East Asian (EAS)

AF:

0.394

AC:

10883

AN:

27602

South Asian (SAS)

AF:

0.217

AC:

9061

AN:

41838

European-Finnish (FIN)

AF:

0.426

AC:

13612

AN:

31950

Middle Eastern (MID)

AF:

0.286

AC:

547

AN:

1912

European-Non Finnish (NFE)

AF:

0.409

AC:

106881

AN:

261202

Other (OTH)

AF:

0.371

AC:

9111

AN:

24576

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

4488

8976

13464

17952

22440

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

536

1072

1608

2144

2680

<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:

0.349

AC:

53099

AN:

151956

Hom.:

9767

Cov.:

AF XY:

0.350

AC XY:

25978

AN XY:

74268

show subpopulations

African (AFR)

AF:

0.229

AC:

9495

AN:

41462

American (AMR)

AF:

0.362

AC:

5538

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.463

AC:

1607

AN:

3470

East Asian (EAS)

AF:

0.406

AC:

2081

AN:

5128

South Asian (SAS)

AF:

0.212

AC:

1021

AN:

4814

European-Finnish (FIN)

AF:

0.424

AC:

4474

AN:

10562

Middle Eastern (MID)

AF:

0.286

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.408

AC:

27684

AN:

67922

Other (OTH)

AF:

0.348

AC:

735

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1706

3411

5117

6822

8528

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

494

988

1482

1976

2470

<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:

0.388

Hom.:

34781

Bravo

AF:

0.343

Asia WGS

AF:

0.264

AC:

915

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

7.4

(source)

DANN

Benign

0.69

PhyloP100

0.52

PromoterAI

0.022

Neutral

(source)

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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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