Variant 13-111153932-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001354046.2(ARHGEF7):c.193G>A(p.Glu65Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000688 in 1,453,358 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ARHGEF7
NM_001354046.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.91

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:

ARHGEF7 (HGNC:):

ARHGEF7 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.31941915).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF7	NM_001354046.2 linkuse as main transcript	c.193G>A	p.Glu65Lys	missense_variant	2/22	ENST00000646102.2	NP_001340975.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGEF7	ENST00000646102.2 linkuse as main transcript	c.193G>A	p.Glu65Lys	missense_variant	2/22		NM_001354046.2	ENSP00000495631.1		A0A2R8YG42

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000427

AC:

AN:

234128

Hom.:

AF XY:

0.00000779

AC XY:

AN XY:

128436

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000335

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1453358

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723220

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 04, 2024

The c.193G>A (p.E65K) alteration is located in exon 2 (coding exon 2) of the ARHGEF7 gene. This alteration results from a G to A substitution at nucleotide position 193, causing the glutamic acid (E) at amino acid position 65 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.92

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.020

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.53

.;D;.

Eigen

Benign

0.025

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.81

LIST_S2

Pathogenic

0.98

D;D;D

M_CAP

Pathogenic

0.37

MetaRNN

Benign

0.32

T;T;T

MetaSVM

Uncertain

0.24

MutationAssessor

Benign

0.020

N;N;.

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-1.2

N;N;.

REVEL

Uncertain

0.47

Sift

Benign

0.037

D;D;.

Sift4G

Uncertain

0.027

D;D;.

Polyphen

0.89

P;P;.

Vest4

0.64

MutPred

0.46

Gain of methylation at E65 (P = 0.0079);Gain of methylation at E65 (P = 0.0079);Gain of methylation at E65 (P = 0.0079);

MVP

0.81

MPC

0.66

ClinPred

0.55

GERP RS

3.8

Varity_R

0.56

gMVP

0.46

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