Genetic Variant RABEP2:c.543+15A>G (chr16-28914657-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_024816.3(RABEP2):c.543+15A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.695 in 1,613,346 control chromosomes in the GnomAD database, including 395,782 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 0.76 ( 44771 hom., cov: 32)

Exomes 𝑓: 0.69 ( 351011 hom. )

Consequence

RABEP2
NM_024816.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.07

Publications

20 publications found

Variant links:

Genes affected

RABEP2 (HGNC:24817): (rabaptin, RAB GTPase binding effector protein 2) Predicted to enable GTPase activator activity and growth factor activity. Involved in regulation of cilium assembly. Located in cytosol; intracellular membrane-bounded organelle; and microtubule organizing center. [provided by Alliance of Genome Resources, Apr 2022]

RABEP2 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 (AFR) allele frequency at 95% confidence interval = 0.931 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RABEP2	NM_024816.3 link	c.543+15A>G		intron_variant	Intron 4 of 12	ENST00000358201.9	NP_079092.2	Q9H5N1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RABEP2	ENST00000358201.9 link	c.543+15A>G		intron_variant	Intron 4 of 12	1	NM_024816.3	ENSP00000350934.4		Q9H5N1-1

Frequencies

GnomAD3 genomes

AF:

0.755

AC:

114817

AN:

151990

Hom.:

44722

Cov.:

show subpopulations

Gnomad AFR

AF:

0.938

Gnomad AMI

AF:

0.802

Gnomad AMR

AF:

0.638

Gnomad ASJ

AF:

0.767

Gnomad EAS

AF:

0.885

Gnomad SAS

AF:

0.827

Gnomad FIN

AF:

0.642

Gnomad MID

AF:

0.810

Gnomad NFE

AF:

0.671

Gnomad OTH

AF:

0.765

GnomAD2 exomes

AF:

0.708

AC:

176070

AN:

248806

AF XY:

0.715

show subpopulations

Gnomad AFR exome

AF:

0.944

Gnomad AMR exome

AF:

0.537

Gnomad ASJ exome

AF:

0.762

Gnomad EAS exome

AF:

0.900

Gnomad FIN exome

AF:

0.638

Gnomad NFE exome

AF:

0.675

Gnomad OTH exome

AF:

0.699

GnomAD4 exome

AF:

0.689

AC:

1006731

AN:

1461240

Hom.:

351011

Cov.:

AF XY:

0.693

AC XY:

503552

AN XY:

726952

show subpopulations

African (AFR)

AF:

0.953

AC:

31903

AN:

33464

American (AMR)

AF:

0.539

AC:

24062

AN:

44668

Ashkenazi Jewish (ASJ)

AF:

0.766

AC:

19995

AN:

26104

East Asian (EAS)

AF:

0.874

AC:

34686

AN:

39696

South Asian (SAS)

AF:

0.818

AC:

70558

AN:

86218

European-Finnish (FIN)

AF:

0.638

AC:

34063

AN:

53350

Middle Eastern (MID)

AF:

0.835

AC:

4815

AN:

5766

European-Non Finnish (NFE)

AF:

0.669

AC:

743263

AN:

1111592

Other (OTH)

AF:

0.719

AC:

43386

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

18366

36732

55097

73463

91829

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19358

38716

58074

77432

96790

<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:

0.755

AC:

114914

AN:

152106

Hom.:

44771

Cov.:

AF XY:

0.755

AC XY:

56127

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.938

AC:

38982

AN:

41544

American (AMR)

AF:

0.637

AC:

9724

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.767

AC:

2659

AN:

3466

East Asian (EAS)

AF:

0.885

AC:

4564

AN:

5158

South Asian (SAS)

AF:

0.827

AC:

3995

AN:

4828

European-Finnish (FIN)

AF:

0.642

AC:

6791

AN:

10580

Middle Eastern (MID)

AF:

0.820

AC:

241

AN:

294

European-Non Finnish (NFE)

AF:

0.671

AC:

45619

AN:

67948

Other (OTH)

AF:

0.763

AC:

1609

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1326

2652

3977

5303

6629

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

844

1688

2532

3376

4220

<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:

0.634

Hom.:

3377

Bravo

AF:

0.761

Asia WGS

AF:

0.798

AC:

2778

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

0.016

(source)

DANN

Benign

0.33

PhyloP100

-1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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