Variant chr8-1857947-TTTTTC-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_014629.4(ARHGEF10):c.38-8_38-4delCTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00498 in 1,610,914 control chromosomes in the GnomAD database, including 64 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0043 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0051 ( 57 hom. )

Consequence

ARHGEF10
NM_014629.4 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.32

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 8-1857947-TTTTTC-T is Benign according to our data. Variant chr8-1857947-TTTTTC-T is described in ClinVar as [Benign]. Clinvar id is 708928.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-1857947-TTTTTC-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.00505 (7374/1458830) while in subpopulation SAS AF= 0.0167 (1438/86140). AF 95% confidence interval is 0.016. There are 57 homozygotes in gnomad4_exome. There are 4018 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

BS2

High AC in GnomAd4 at 648 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF10	NM_014629.4 link	c.38-8_38-4delCTTTT		splice_region_variant, 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.38-12_38-8delTTTTC		splice_region_variant, intron_variant		1	NM_014629.4	ENSP00000340297.3		O15013-5
KBTBD11-OT1	ENST00000635855.1 link	n.628-12_628-8delTTTTC		splice_region_variant, intron_variant		5		ENSP00000489726.1		A0A1B0GTJ5

Frequencies

GnomAD3 genomes

AF:

0.00426

AC:

647

AN:

151966

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000846

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00479

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0129

Gnomad FIN

AF:

0.0133

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00472

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00599

AC:

1502

AN:

250580

Hom.:

AF XY:

0.00671

AC XY:

909

AN XY:

135500

show subpopulations

Gnomad AFR exome

AF:

0.000743

Gnomad AMR exome

AF:

0.00272

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.000436

Gnomad SAS exome

AF:

0.0155

Gnomad FIN exome

AF:

0.0120

Gnomad NFE exome

AF:

0.00533

Gnomad OTH exome

AF:

0.00800

GnomAD4 exome

AF:

0.00505

AC:

7374

AN:

1458830

Hom.:

AF XY:

0.00553

AC XY:

4018

AN XY:

725974

show subpopulations

Gnomad4 AFR exome

AF:

0.000628

Gnomad4 AMR exome

AF:

0.00259

Gnomad4 ASJ exome

AF:

0.000421

Gnomad4 EAS exome

AF:

0.000328

Gnomad4 SAS exome

AF:

0.0167

Gnomad4 FIN exome

AF:

0.0123

Gnomad4 NFE exome

AF:

0.00426

Gnomad4 OTH exome

AF:

0.00511

GnomAD4 genome

AF:

0.00426

AC:

648

AN:

152084

Hom.:

Cov.:

AF XY:

0.00452

AC XY:

336

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.000843

Gnomad4 AMR

AF:

0.00478

Gnomad4 ASJ

AF:

0.000289

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.0131

Gnomad4 FIN

AF:

0.0133

Gnomad4 NFE

AF:

0.00472

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00299

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 24, 2024

- -

ARHGEF10-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 24, 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

Splicing

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