Variant 8-1843496-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014629.4(ARHGEF10):c.37+60C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,337,902 control chromosomes in the GnomAD database, including 10,303 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1152 hom., cov: 32)

Exomes 𝑓: 0.11 ( 9151 hom. )

Consequence

ARHGEF10
NM_014629.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.70

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:

KBTBD11-OT1 (HGNC:):

KBTBD11-OT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 8-1843496-C-T is Benign according to our data. Variant chr8-1843496-C-T is described in ClinVar as [Benign]. Clinvar id is 1288449.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF10	NM_014629.4 link	c.37+60C>T		intron_variant		ENST00000349830.8	NP_055444.2	O15013-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGEF10	ENST00000349830.8 link	c.37+60C>T		intron_variant		1	NM_014629.4	ENSP00000340297.3		O15013-5
KBTBD11-OT1	ENST00000635855.1 link	n.627+60C>T		intron_variant		5		ENSP00000489726.1		A0A1B0GTJ5

Frequencies

GnomAD3 genomes

AF:

0.113

AC:

17235

AN:

151986

Hom.:

1145

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0875

Gnomad AMI

AF:

0.0811

Gnomad AMR

AF:

0.204

Gnomad ASJ

AF:

0.0926

Gnomad EAS

AF:

0.240

Gnomad SAS

AF:

0.180

Gnomad FIN

AF:

0.102

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.0973

Gnomad OTH

AF:

0.125

GnomAD4 exome

AF:

0.114

AC:

135082

AN:

1185798

Hom.:

9151

AF XY:

0.116

AC XY:

70029

AN XY:

601588

show subpopulations

Gnomad4 AFR exome

AF:

0.0856

Gnomad4 AMR exome

AF:

0.237

Gnomad4 ASJ exome

AF:

0.0978

Gnomad4 EAS exome

AF:

0.261

Gnomad4 SAS exome

AF:

0.179

Gnomad4 FIN exome

AF:

0.0895

Gnomad4 NFE exome

AF:

0.0983

Gnomad4 OTH exome

AF:

0.118

GnomAD4 genome

AF:

0.114

AC:

17272

AN:

152104

Hom.:

1152

Cov.:

AF XY:

0.118

AC XY:

8808

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.0881

Gnomad4 AMR

AF:

0.204

Gnomad4 ASJ

AF:

0.0926

Gnomad4 EAS

AF:

0.239

Gnomad4 SAS

AF:

0.180

Gnomad4 FIN

AF:

0.102

Gnomad4 NFE

AF:

0.0973

Gnomad4 OTH

AF:

0.125

Alfa

AF:

0.0998

Hom.:

170

Bravo

AF:

0.123

Asia WGS

AF:

0.195

AC:

680

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 11, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

6.7

DANN

Benign

0.43

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