11-3828006-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001665.4(RHOG):c.133G>A(p.Ala45Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00153 in 1,614,276 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 5 hom. )

Consequence

RHOG
NM_001665.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.33

Variant links:

Genes affected

RHOG (HGNC:672): (ras homolog family member G) This gene encodes a member of the Rho family of small GTPases, which cycle between inactive GDP-bound and active GTP-bound states and function as molecular switches in signal transduction cascades. Rho proteins promote reorganization of the actin cytoskeleton and regulate cell shape, attachment, and motility. The encoded protein facilitates translocation of a functional guanine nucleotide exchange factor (GEF) complex from the cytoplasm to the plasma membrane where ras-related C3 botulinum toxin substrate 1 is activated to promote lamellipodium formation and cell migration. Two related pseudogene have been identified on chromosomes 20 and X. [provided by RefSeq, Aug 2011]

RHOG links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008496374).

BP6

Variant 11-3828006-C-T is Benign according to our data. Variant chr11-3828006-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3350246.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 157 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHOG	NM_001665.4 link	c.133G>A	p.Ala45Thr	missense_variant	Exon 2 of 2	ENST00000351018.5	NP_001656.2	P84095Q6ICQ8
RHOG	XM_005252916.3 link	c.133G>A	p.Ala45Thr	missense_variant	Exon 2 of 2		XP_005252973.1	P84095Q6ICQ8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RHOG	ENST00000351018.5 link	c.133G>A	p.Ala45Thr	missense_variant	Exon 2 of 2	1	NM_001665.4	ENSP00000339467.4	P84095
RHOG	ENST00000396978.1 link	c.133G>A	p.Ala45Thr	missense_variant	Exon 2 of 2	3		ENSP00000380175.1	P84095
RHOG	ENST00000396979.1 link	c.133G>A	p.Ala45Thr	missense_variant	Exon 2 of 2	3		ENSP00000380176.1	P84095
RHOG	ENST00000533217.1 link	c.133G>A	p.Ala45Thr	missense_variant	Exon 2 of 2	5		ENSP00000436932.1	P84095

Frequencies

GnomAD3 genomes

AF:

0.00103

AC:

157

AN:

152268

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.000392

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00197

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00115

AC:

289

AN:

251470

Hom.:

AF XY:

0.00116

AC XY:

157

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.000491

Gnomad ASJ exome

AF:

0.000198

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00214

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00158

AC:

2307

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00160

AC XY:

1161

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000559

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000209

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.00197

Gnomad4 OTH exome

AF:

0.000861

GnomAD4 genome

AF:

0.00103

AC:

157

AN:

152386

Hom.:

Cov.:

AF XY:

0.000993

AC XY:

AN XY:

74522

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00197

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00201

Hom.:

Bravo

AF:

0.00126

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00163

AC:

ExAC

AF:

0.00108

AC:

131

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00125

EpiControl

AF:

0.00154

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

RHOG-related condition

Benign:1

Apr 29, 2024

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.54

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.18

T;T;T;T

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.29

FATHMM_MKL

Uncertain

0.77

LIST_S2

Uncertain

0.87

.;.;.;D

M_CAP

Benign

0.015

MetaRNN

Benign

0.0085

T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-1.8

N;N;N;N

PrimateAI

Uncertain

0.59

PROVEAN

Benign

0.17

N;N;N;N

REVEL

Benign

0.21

Sift

Benign

0.16

T;T;T;T

Sift4G

Benign

0.44

T;T;T;T

Polyphen

0.0010

B;B;B;B

Vest4

0.018

MVP

0.34

MPC

1.2

ClinPred

0.014

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.085

gMVP

0.26

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