Genetic Variant RABEP1:p.Ser8Pro (chr17-5282508-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_004703.6(RABEP1):c.22T>C(p.Ser8Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000271 in 1,106,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

RABEP1
NM_004703.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.217

Publications

0 publications found

Variant links:

Genes affected

RABEP1 (HGNC:17677): (rabaptin, RAB GTPase binding effector protein 1) Enables protein domain specific binding activity and protein homodimerization activity. Involved in vesicle-mediated transport. Located in endocytic vesicle and endosome. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

RABEP1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.053823113).

BP6

Variant 17-5282508-T-C is Benign according to our data. Variant chr17-5282508-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2534515.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004703.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RABEP1	NM_004703.6	MANE Select	c.22T>C	p.Ser8Pro	missense	Exon 1 of 18	NP_004694.2
RABEP1	NM_001083585.3		c.22T>C	p.Ser8Pro	missense	Exon 1 of 17	NP_001077054.1	Q15276-2
RABEP1	NM_001291581.2		c.22T>C	p.Ser8Pro	missense	Exon 1 of 17	NP_001278510.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RABEP1	ENST00000537505.6	TSL:1 MANE Select	c.22T>C	p.Ser8Pro	missense	Exon 1 of 18	ENSP00000445408.2	Q15276-1
RABEP1	ENST00000341923.10	TSL:1	c.22T>C	p.Ser8Pro	missense	Exon 1 of 17	ENSP00000339569.6	Q15276-2
RABEP1	ENST00000575475.2	TSL:1	n.187T>C		non_coding_transcript_exon	Exon 1 of 14

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000271

AC:

AN:

1106078

Hom.:

Cov.:

AF XY:

0.00000189

AC XY:

AN XY:

530224

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22894

American (AMR)

AF:

0.00

AC:

AN:

10248

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15330

East Asian (EAS)

AF:

0.00

AC:

AN:

25968

South Asian (SAS)

AF:

0.00

AC:

AN:

29268

European-Finnish (FIN)

AF:

0.00

AC:

AN:

22642

Middle Eastern (MID)

AF:

0.000332

AC:

AN:

3012

European-Non Finnish (NFE)

AF:

0.00000214

AC:

AN:

932578

Other (OTH)

AF:

0.00

AC:

AN:

44138

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.408

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

Cov.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.045

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.0062

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.052

LIST_S2

Benign

0.18

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.054

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.55

PhyloP100

-0.22

PrimateAI

Uncertain

0.74

PROVEAN

Benign

0.28

REVEL

Benign

0.086

Sift

Benign

0.28

Sift4G

Benign

0.34

Polyphen

0.0

Vest4

0.072

MutPred

0.13

Loss of phosphorylation at S8 (P = 0.0217)

MVP

0.18

ClinPred

0.096

GERP RS

-0.053

PromoterAI

-0.025

Neutral

(source)

Varity_R

0.11

gMVP

0.12

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over