Genetic Variant RABEP2:p.Val491Met (chr16-28905724-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024816.3(RABEP2):c.1471G>A(p.Val491Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000206 in 1,614,030 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0012 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

RABEP2
NM_024816.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.552

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0074278414).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RABEP2	NM_024816.3 link	c.1471G>A	p.Val491Met	missense_variant	Exon 11 of 13	ENST00000358201.9	NP_079092.2	Q9H5N1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RABEP2	ENST00000358201.9 link	c.1471G>A	p.Val491Met	missense_variant	Exon 11 of 13	1	NM_024816.3	ENSP00000350934.4	Q9H5N1-1
RABEP2	ENST00000357573.10 link	c.1363G>A	p.Val455Met	missense_variant	Exon 9 of 11	1		ENSP00000350186.6	Q9H5N1-2
RABEP2	ENST00000544477.5 link	c.1258G>A	p.Val420Met	missense_variant	Exon 10 of 12	2		ENSP00000442798.1	B4DHR0

Frequencies

GnomAD3 genomes

AF:

0.00123

AC:

187

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00429

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000392

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000306

AC:

AN:

248722

Hom.:

AF XY:

0.000244

AC XY:

AN XY:

135066

show subpopulations

Gnomad AFR exome

AF:

0.00428

Gnomad AMR exome

AF:

0.000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000999

AC:

146

AN:

1461690

Hom.:

Cov.:

AF XY:

0.0000798

AC XY:

AN XY:

727136

show subpopulations

Gnomad4 AFR exome

AF:

0.00385

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.00123

AC:

187

AN:

152340

Hom.:

Cov.:

AF XY:

0.00113

AC XY:

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00428

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.0000141

Hom.:

Bravo

AF:

0.00116

ESP6500AA

AF:

0.00441

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000364

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

.;T;.

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.78

T;T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.0074

T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

1.2

.;L;.

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.92

N;N;N

REVEL

Benign

0.086

Sift

Uncertain

0.0040

D;D;D

Sift4G

Benign

0.19

T;T;T

Polyphen

0.88

P;B;P

Vest4

0.28

MVP

0.34

MPC

0.18

ClinPred

0.074

GERP RS

-6.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.049

gMVP

0.071

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over