Variant 13-111153917-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BS2

The NM_001354046.2(ARHGEF7):c.178C>G(p.Pro60Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000344 in 1,452,904 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

ARHGEF7
NM_001354046.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.69

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BS2

High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGEF7	NM_001354046.2 linkuse as main transcript	c.178C>G	p.Pro60Ala	missense_variant	2/22	ENST00000646102.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGEF7	ENST00000646102.2 linkuse as main transcript	c.178C>G	p.Pro60Ala	missense_variant	2/22		NM_001354046.2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000214

AC:

AN:

233644

Hom.:

AF XY:

0.0000156

AC XY:

AN XY:

128244

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000300

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000344

AC:

AN:

1452904

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723040

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000130

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000826

AC:

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

Aug 30, 2021

The c.178C>G (p.P60A) alteration is located in exon 2 (coding exon 2) of the ARHGEF7 gene. This alteration results from a C to G substitution at nucleotide position 178, causing the proline (P) at amino acid position 60 to be replaced by an alanine (A). 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

0.77

BayesDel_addAF

Benign

-0.031

BayesDel_noAF

Uncertain

0.020

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.80

.;D;.

Eigen

Benign

0.16

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.82

T;T;T

M_CAP

Pathogenic

0.85

MetaRNN

Uncertain

0.51

D;D;D

MetaSVM

Pathogenic

0.97

MutationAssessor

Uncertain

2.9

M;M;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;N

PrimateAI

Pathogenic

0.86

PROVEAN

Uncertain

-2.9

D;D;.

REVEL

Pathogenic

0.71

Sift

Benign

0.037

D;D;.

Sift4G

Uncertain

0.027

D;D;.

Polyphen

0.23

B;P;.

Vest4

0.52

MutPred

0.51

Loss of glycosylation at P60 (P = 0.0236);Loss of glycosylation at P60 (P = 0.0236);Loss of glycosylation at P60 (P = 0.0236);

MVP

0.89

MPC

0.67

ClinPred

0.70

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.21

gMVP

0.35

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