rs7003839

chr8-1869148-G-Cchr8-1869148-G-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.623-46G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 1,550,380 control chromosomes in the GnomAD database, including 39,500 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.20 (3316 hom., cov: 33)
  • Exomes 𝑓: 0.22 (36184 hom.)
• Consequence: ARHGEF10 NM_014629.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.965

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=-0.94).
• BP6: Variant 8-1869148-G-C is Benign according to our data. Variant chr8-1869148-G-C is described in ClinVar as [Benign]. Clinvar id is 1235723.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGEF10	NM_014629.4	c.623-46G>C		intron_variant		ENST00000349830.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGEF10	ENST00000349830.8	c.623-46G>C		intron_variant		1	NM_014629.4	P4

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29955 AN: 151962 Hom.: 3309 Cov.: 33

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.361

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.176

GnomAD3 exomes AF: 0.227 AC: 57048 AN: 251270 Hom.: 7016 AF XY: 0.223 AC XY: 30254 AN XY: 135820

Gnomad AFR exome AF: 0.0929

Gnomad AMR exome AF: 0.259

Gnomad ASJ exome AF: 0.216

Gnomad EAS exome AF: 0.356

Gnomad SAS exome AF: 0.164

Gnomad FIN exome AF: 0.256

Gnomad NFE exome AF: 0.229

Gnomad OTH exome AF: 0.220

GnomAD4 exome AF: 0.224 AC: 312532 AN: 1398300 Hom.: 36184 Cov.: 24 AF XY: 0.221 AC XY: 154876 AN XY: 699494

Gnomad4 AFR exome AF: 0.0924

Gnomad4 AMR exome AF: 0.252

Gnomad4 ASJ exome AF: 0.220

Gnomad4 EAS exome AF: 0.340

Gnomad4 SAS exome AF: 0.163

Gnomad4 FIN exome AF: 0.251

Gnomad4 NFE exome AF: 0.227

Gnomad4 OTH exome AF: 0.211

GnomAD4 genome AF: 0.197 AC: 29993 AN: 152080 Hom.: 3316 Cov.: 33 AF XY: 0.199 AC XY: 14768 AN XY: 74338

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.213

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.361

Gnomad4 SAS AF: 0.178

Gnomad4 FIN AF: 0.247

Gnomad4 NFE AF: 0.232

Gnomad4 OTH AF: 0.179

Alfa AF: 0.219 Hom.: 653

Bravo AF: 0.193

Asia WGS AF: 0.252 AC: 876 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 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.16
Dann	Benign	0.33

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: rs7003839; hg19: chr8-1817314; COSMIC: COSV50667880;