8-1928465-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_014629.4(ARHGEF10):c.2736C>T(p.Ile912Ile) 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

Publications

19 publications found

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 Gene-Disease associations (from GenCC):

autosomal dominant slowed nerve conduction velocity
Inheritance: Unknown, AD Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet
hereditary peripheral neuropathy
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
peripheral neuropathy
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ARHGEF10 links:

KBTBD11-OT1 (HGNC:):

KBTBD11-OT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 1282318.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
ARHGEF10	NM_014629.4 link	c.2736C>T	p.Ile912Ile	synonymous_variant	Exon 24 of 29	ENST00000349830.8	NP_055444.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
ARHGEF10	ENST00000349830.8 link	c.2736C>T	p.Ile912Ile	synonymous_variant	Exon 24 of 29	1	NM_014629.4	ENSP00000340297.3
KBTBD11-OT1	ENST00000635855.1 link	n.*2690C>T		non_coding_transcript_exon_variant	Exon 25 of 30	5		ENSP00000489726.1
KBTBD11-OT1	ENST00000635855.1 link	n.*2690C>T		3_prime_UTR_variant	Exon 25 of 30	5		ENSP00000489726.1

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

GnomAD2 exomes

AF:

0.161

AC:

40456

AN:

251480

AF XY:

0.157

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 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

African (AFR)

AF:

0.119

AC:

3959

AN:

33394

American (AMR)

AF:

0.243

AC:

10857

AN:

44672

Ashkenazi Jewish (ASJ)

AF:

0.148

AC:

3871

AN:

26088

East Asian (EAS)

AF:

0.181

AC:

7144

AN:

39570

South Asian (SAS)

AF:

0.138

AC:

11877

AN:

86234

European-Finnish (FIN)

AF:

0.177

AC:

9445

AN:

53240

Middle Eastern (MID)

AF:

0.126

AC:

726

AN:

5762

European-Non Finnish (NFE)

AF:

0.140

AC:

156059

AN:

1110996

Other (OTH)

AF:

0.139

AC:

8348

AN:

60274

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

10687

21373

32060

42746

53433

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5728

11456

17184

22912

28640

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.142

AC:

21647

AN:

151956

Hom.:

1566

Cov.:

AF XY:

0.145

AC XY:

10768

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.120

AC:

4951

AN:

41428

American (AMR)

AF:

0.184

AC:

2810

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.151

AC:

522

AN:

3468

East Asian (EAS)

AF:

0.176

AC:

906

AN:

5148

South Asian (SAS)

AF:

0.134

AC:

642

AN:

4794

European-Finnish (FIN)

AF:

0.182

AC:

1919

AN:

10556

Middle Eastern (MID)

AF:

0.112

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.139

AC:

9429

AN:

67976

Other (OTH)

AF:

0.131

AC:

276

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

965

1929

2894

3858

4823

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

236

472

708

944

1180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.141

Hom.:

3872

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

ARHGEF10-related disorder

Benign:1

Mar 18, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

(source)

DANN

Benign

0.67

PhyloP100

-0.32

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over