Variant chr13-111209997-A-T 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.463A>T(p.Ser155Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00221 in 1,614,080 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0013 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0023 ( 4 hom. )

Consequence

ARHGEF7
NM_001354046.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 8.44

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=0.01188007).

BP6

Variant 13-111209997-A-T is Benign according to our data. Variant chr13-111209997-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 718926.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr13-111209997-A-T is described in Lovd as [Likely_benign].

BS2

High AC in GnomAd4 at 201 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGEF7	NM_001354046.2 linkuse as main transcript	c.463A>T	p.Ser155Cys	missense_variant	4/22	ENST00000646102.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGEF7	ENST00000646102.2 linkuse as main transcript	c.463A>T	p.Ser155Cys	missense_variant	4/22		NM_001354046.2

Frequencies

GnomAD3 genomes

AF:

0.00132

AC:

201

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000387

Gnomad AMI

AF:

0.0198

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00223

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00109

AC:

273

AN:

251478

Hom.:

AF XY:

0.00108

AC XY:

147

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00188

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.00208

Gnomad OTH exome

AF:

0.000978

GnomAD4 exome

AF:

0.00231

AC:

3372

AN:

1461872

Hom.:

Cov.:

AF XY:

0.00222

AC XY:

1613

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.000568

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.00172

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.000300

Gnomad4 NFE exome

AF:

0.00288

Gnomad4 OTH exome

AF:

0.00136

GnomAD4 genome

AF:

0.00132

AC:

201

AN:

152208

Hom.:

Cov.:

AF XY:

0.00102

AC XY:

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.000385

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.00223

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00215

Hom.:

Bravo

AF:

0.00148

TwinsUK

AF:

0.00405

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00279

AC:

ExAC

AF:

0.000947

AC:

115

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00218

EpiControl

AF:

0.00148

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

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.34

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Uncertain

-0.020

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.33

.;.;T;.;T

Eigen

Uncertain

0.64

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

D;D;D;D;D

M_CAP

Benign

0.024

MetaRNN

Benign

0.012

T;T;T;T;T

MetaSVM

Benign

-0.63

MutationAssessor

Uncertain

2.3

.;.;M;.;.

MutationTaster

Benign

1.0

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

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.4

N;N;N;.;N

REVEL

Benign

0.24

Sift

Uncertain

0.012

D;D;D;.;D

Sift4G

Uncertain

0.0040

D;D;D;.;D

Polyphen

1.0

D;D;D;.;.

Vest4

0.81

MVP

0.66

MPC

1.5

ClinPred

0.12

GERP RS

5.4

Varity_R

0.34

gMVP

0.66

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