Variant chr8-1928465-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_014629.4(ARHGEF10):c.2736C>T(p.Ile912=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,612,186 control chromosomes in the GnomAD database, including 17,512 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1566 hom., cov: 33)

Exomes 𝑓: 0.15 ( 15946 hom. )

Consequence

ARHGEF10
NM_014629.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.317

Variant links:

Genes affected

ARHGEF10 (HGNC:14103): (Rho guanine nucleotide exchange factor 10) This gene encodes a Rho guanine nucleotide exchange factor (GEF). Rho GEFs regulate the activity of small Rho GTPases by stimulating the exchange of guanine diphosphate (GDP) for guanine triphosphate (GTP) and may play a role in neural morphogenesis. Mutations in this gene are associated with slowed nerve conduction velocity (SNCV). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

ARHGEF10 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 8-1928465-C-T is Benign according to our data. Variant chr8-1928465-C-T is described in ClinVar as [Benign]. Clinvar id is 1282318.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-1928465-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.317 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGEF10	NM_014629.4 linkuse as main transcript	c.2736C>T	p.Ile912=	synonymous_variant	24/29	ENST00000349830.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGEF10	ENST00000349830.8 linkuse as main transcript	c.2736C>T	p.Ile912=	synonymous_variant	24/29	1	NM_014629.4	P4	O15013-5

Frequencies

GnomAD3 genomes

AF:

0.143

AC:

21645

AN:

151838

Hom.:

1567

Cov.:

show subpopulations

Gnomad AFR

AF:

0.120

Gnomad AMI

AF:

0.174

Gnomad AMR

AF:

0.184

Gnomad ASJ

AF:

0.151

Gnomad EAS

AF:

0.175

Gnomad SAS

AF:

0.135

Gnomad FIN

AF:

0.182

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.139

Gnomad OTH

AF:

0.133

GnomAD3 exomes

AF:

0.161

AC:

40456

AN:

251480

Hom.:

3576

AF XY:

0.157

AC XY:

21385

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.118

Gnomad AMR exome

AF:

0.250

Gnomad ASJ exome

AF:

0.149

Gnomad EAS exome

AF:

0.168

Gnomad SAS exome

AF:

0.140

Gnomad FIN exome

AF:

0.179

Gnomad NFE exome

AF:

0.142

Gnomad OTH exome

AF:

0.156

GnomAD4 exome

AF:

0.145

AC:

212286

AN:

1460230

Hom.:

15946

Cov.:

AF XY:

0.144

AC XY:

104807

AN XY:

726486

show subpopulations

Gnomad4 AFR exome

AF:

0.119

Gnomad4 AMR exome

AF:

0.243

Gnomad4 ASJ exome

AF:

0.148

Gnomad4 EAS exome

AF:

0.181

Gnomad4 SAS exome

AF:

0.138

Gnomad4 FIN exome

AF:

0.177

Gnomad4 NFE exome

AF:

0.140

Gnomad4 OTH exome

AF:

0.139

GnomAD4 genome

AF:

0.142

AC:

21647

AN:

151956

Hom.:

1566

Cov.:

AF XY:

0.145

AC XY:

10768

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.120

Gnomad4 AMR

AF:

0.184

Gnomad4 ASJ

AF:

0.151

Gnomad4 EAS

AF:

0.176

Gnomad4 SAS

AF:

0.134

Gnomad4 FIN

AF:

0.182

Gnomad4 NFE

AF:

0.139

Gnomad4 OTH

AF:

0.131

Alfa

AF:

0.139

Hom.:

2767

Bravo

AF:

0.145

Asia WGS

AF:

0.152

AC:

529

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

ARHGEF10-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 18, 2019

This variant is classified as 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

BayesDel_noAF

Benign

-0.54

CADD

Benign

4.7

DANN

Benign

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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