Variant 13-111217801-G-C 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_001354046.2(ARHGEF7):c.591G>C(p.Glu197Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000906 in 1,614,244 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00086 ( 6 hom. )

Consequence

ARHGEF7
NM_001354046.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.309

Variant links:

Genes affected

ARHGEF7 (HGNC:15607): (Rho guanine nucleotide exchange factor 7) This gene encodes a protein that belongs to a family of cytoplasmic proteins that activate the Ras-like family of Rho proteins by exchanging bound GDP for GTP. It forms a complex with the small GTP binding protein Rac1 and recruits Rac1 to membrane ruffles and to focal adhesions. Multiple alternatively spliced transcript variants encoding different isoforms have been observed for this gene. [provided by RefSeq, Mar 2016]

ARHGEF7 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=0.0075306892).

BP6

Variant 13-111217801-G-C is Benign according to our data. Variant chr13-111217801-G-C is described in ClinVar as [Benign]. Clinvar id is 790371.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 211 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGEF7	NM_001354046.2 linkuse as main transcript	c.591G>C	p.Glu197Asp	missense_variant	5/22	ENST00000646102.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGEF7	ENST00000646102.2 linkuse as main transcript	c.591G>C	p.Glu197Asp	missense_variant	5/22		NM_001354046.2

Frequencies

GnomAD3 genomes

AF:

0.00139

AC:

211

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000723

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00405

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00404

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00932

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00221

AC:

555

AN:

251472

Hom.:

AF XY:

0.00184

AC XY:

250

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00836

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00136

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00748

Gnomad NFE exome

AF:

0.000466

Gnomad OTH exome

AF:

0.00342

GnomAD4 exome

AF:

0.000856

AC:

1252

AN:

1461876

Hom.:

Cov.:

AF XY:

0.000759

AC XY:

552

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00800

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00539

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.00702

Gnomad4 NFE exome

AF:

0.000202

Gnomad4 OTH exome

AF:

0.00106

GnomAD4 genome

AF:

0.00138

AC:

211

AN:

152368

Hom.:

Cov.:

AF XY:

0.00176

AC XY:

131

AN XY:

74522

show subpopulations

Gnomad4 AFR

AF:

0.0000721

Gnomad4 AMR

AF:

0.00411

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00405

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00932

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000401

Hom.:

Bravo

AF:

0.00111

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00202

AC:

245

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

.;.;T;.;.;T;T;.;T;.;T;.

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.41

FATHMM_MKL

Uncertain

0.76

LIST_S2

Uncertain

0.91

D;D;D;D;D;D;D;.;D;D;D;D

MetaRNN

Benign

0.0075

T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.72

.;.;N;.;.;.;.;.;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D;D;D

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.2

N;N;N;N;.;N;N;N;N;N;N;N

REVEL

Benign

0.15

Sift

Benign

0.20

T;T;T;T;.;T;T;T;T;T;T;T

Sift4G

Benign

0.57

T;T;T;T;.;T;T;T;T;T;T;T

Polyphen

0.33

B;B;B;.;.;.;.;.;.;.;.;.

Vest4

0.22

MutPred

0.34

.;.;Gain of loop (P = 0.2754);.;.;.;.;.;.;.;.;.;

MVP

0.52

MPC

0.61

ClinPred

0.039

GERP RS

-0.33

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.63

gMVP

0.29

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