Variant 1-156065926-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_020387.4(RAB25):c.59A>G(p.Glu20Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.006 in 1,603,352 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0049 ( 5 hom., cov: 31)

Exomes 𝑓: 0.0061 ( 36 hom. )

Consequence

RAB25
NM_020387.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 9.20

Variant links:

Genes affected

RAB25 (HGNC:18238): (RAB25, member RAS oncogene family) The protein encoded by this gene is a member of the RAS superfamily of small GTPases. The encoded protein is involved in membrane trafficking and cell survival. This gene has been found to be a tumor suppressor and an oncogene, depending on the context. Two variants, one protein-coding and the other not, have been found for this gene. [provided by RefSeq, Nov 2015]

RAB25 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014712751).

BP6

Variant 1-156065926-A-G is Benign according to our data. Variant chr1-156065926-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3234162.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-156065926-A-G is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB25	NM_020387.4 linkuse as main transcript	c.59A>G	p.Glu20Gly	missense_variant	2/5	ENST00000361084.10
RAB25	NR_133653.2 linkuse as main transcript	n.285-2344A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
RAB25	ENST00000361084.10 linkuse as main transcript	c.59A>G	p.Glu20Gly	missense_variant	2/5	1	NM_020387.4	P1
RAB25	ENST00000463614.1 linkuse as main transcript	n.271A>G		non_coding_transcript_exon_variant	2/2	2
RAB25	ENST00000473336.5 linkuse as main transcript	n.62-2344A>G		intron_variant, non_coding_transcript_variant		2
RAB25	ENST00000487325.5 linkuse as main transcript	n.239-2344A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00487

AC:

740

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000797

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00622

Gnomad ASJ

AF:

0.0184

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.000378

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00773

Gnomad OTH

AF:

0.00576

GnomAD3 exomes

AF:

0.00489

AC:

1195

AN:

244396

Hom.:

AF XY:

0.00495

AC XY:

655

AN XY:

132374

show subpopulations

Gnomad AFR exome

AF:

0.000650

Gnomad AMR exome

AF:

0.00472

Gnomad ASJ exome

AF:

0.0218

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000169

Gnomad FIN exome

AF:

0.000282

Gnomad NFE exome

AF:

0.00694

Gnomad OTH exome

AF:

0.00560

GnomAD4 exome

AF:

0.00612

AC:

8875

AN:

1451148

Hom.:

Cov.:

AF XY:

0.00602

AC XY:

4340

AN XY:

720840

show subpopulations

Gnomad4 AFR exome

AF:

0.000930

Gnomad4 AMR exome

AF:

0.00478

Gnomad4 ASJ exome

AF:

0.0200

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000259

Gnomad4 FIN exome

AF:

0.000546

Gnomad4 NFE exome

AF:

0.00686

Gnomad4 OTH exome

AF:

0.00726

GnomAD4 genome

AF:

0.00486

AC:

740

AN:

152204

Hom.:

Cov.:

AF XY:

0.00461

AC XY:

343

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.000795

Gnomad4 AMR

AF:

0.00621

Gnomad4 ASJ

AF:

0.0184

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.000378

Gnomad4 NFE

AF:

0.00773

Gnomad4 OTH

AF:

0.00570

Alfa

AF:

0.00777

Hom.:

Bravo

AF:

0.00510

TwinsUK

AF:

0.00701

AC:

ALSPAC

AF:

0.00856

AC:

ESP6500AA

AF:

0.000707

AC:

ESP6500EA

AF:

0.00848

AC:

ExAC

AF:

0.00460

AC:

557

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00813

EpiControl

AF:

0.00767

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2024

RAB25: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.82

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Uncertain

-0.050

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.64

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.77

MetaRNN

Benign

0.015

MetaSVM

Uncertain

0.0064

MutationAssessor

Benign

1.6

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-3.2

REVEL

Pathogenic

0.70

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.74

MVP

0.94

MPC

0.69

ClinPred

0.025

GERP RS

5.3

Varity_R

0.91

gMVP

0.87

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over