rs3735875

chr8-1876247-G-Achr8-1876247-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014629.4(ARHGEF10):c.680-324G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 381,734 control chromosomes in the GnomAD database, including 11,419 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.24 (4665 hom., cov: 34)
  • Exomes 𝑓: 0.23 (6754 hom.)
• Consequence: ARHGEF10 NM_014629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGEF10	NM_014629.4	c.680-324G>A		intron_variant		ENST00000349830.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGEF10	ENST00000349830.8	c.680-324G>A		intron_variant		1	NM_014629.4	P4

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36585 AN: 152008 Hom.: 4645 Cov.: 34

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.229

GnomAD4 exome AF: 0.228 AC: 52450 AN: 229608 Hom.: 6754 Cov.: 0 AF XY: 0.222 AC XY: 26529 AN XY: 119762

Gnomad4 AFR exome AF: 0.193

Gnomad4 AMR exome AF: 0.392

Gnomad4 ASJ exome AF: 0.184

Gnomad4 EAS exome AF: 0.343

Gnomad4 SAS exome AF: 0.159

Gnomad4 FIN exome AF: 0.289

Gnomad4 NFE exome AF: 0.222

Gnomad4 OTH exome AF: 0.216

GnomAD4 genome AF: 0.241 AC: 36657 AN: 152126 Hom.: 4665 Cov.: 34 AF XY: 0.244 AC XY: 18122 AN XY: 74350

Gnomad4 AFR AF: 0.206

Gnomad4 AMR AF: 0.337

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.359

Gnomad4 SAS AF: 0.182

Gnomad4 FIN AF: 0.291

Gnomad4 NFE AF: 0.232

Gnomad4 OTH AF: 0.232

Alfa AF: 0.238 Hom.: 964

Bravo AF: 0.248

Asia WGS AF: 0.289 AC: 1004 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.063
Dann	Benign	0.67

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: rs3735875; hg19: chr8-1824413;