rs2280823

Positions:

• chr8-1949491-A-G
• chr8-1949491-A-T

Variant summary

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

The NM_014629.4(ARHGEF10):​c.3398-3214A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,096 control chromosomes in the GnomAD database, including 1,966 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 0.16 (1966 hom., cov: 32)
• Consequence: ARHGEF10 NM_014629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00100

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=-0.87).
• 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.3398-3214A>G		intron_variant		ENST00000349830.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGEF10	ENST00000349830.8	c.3398-3214A>G		intron_variant		1	NM_014629.4	P4

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24203 AN: 151978 Hom.: 1969 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.147

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.159 AC: 24207 AN: 152096 Hom.: 1966 Cov.: 32 AF XY: 0.163 AC XY: 12115 AN XY: 74322

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.195

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.239

Gnomad4 SAS AF: 0.187

Gnomad4 FIN AF: 0.225

Gnomad4 NFE AF: 0.155

Gnomad4 OTH AF: 0.146

Alfa AF: 0.150 Hom.: 2941

Bravo AF: 0.158

Asia WGS AF: 0.197 AC: 682 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.7
DANN	Benign	0.34

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: rs2280823; hg19: chr8-1897657;