8-1843496-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.70

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	UniProt
ARHGEF10	NM_014629.4	c.37+60C>T		intron_variant		ENST00000349830.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGEF10	ENST00000349830.8	c.37+60C>T		intron_variant		1	NM_014629.4	P4
ARHGEF10	ENST00000518288.5	c.109+60C>T		intron_variant		1
ARHGEF10	ENST00000520359.5	c.37+60C>T		intron_variant		1		A2
ARHGEF10	ENST00000398564.5	c.109+60C>T		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17235 AN: 151986 Hom.: 1145 Cov.: 32

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

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.: 32 AF XY: 0.118 AC XY: 8808 AN XY: 74334

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 11, 2021

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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

Other links and lift over

dbSNP: rs74415378; hg19: chr8-1791662; COSMIC: COSV50697265;