chr8-1872490-G-T

Position:

• chr8-1872490-G-T

Variant summary

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

The NM_014629.4(ARHGEF10):​c.679+3240G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 152,102 control chromosomes in the GnomAD database, including 4,155 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 0.23 (4155 hom., cov: 33)
• Consequence: ARHGEF10 NM_014629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF10	NM_014629.4	c.679+3240G>T		intron_variant		ENST00000349830.8	NP_055444.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGEF10	ENST00000349830.8	c.679+3240G>T		intron_variant		1	NM_014629.4	ENSP00000340297	P4

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34866 AN: 151984 Hom.: 4139 Cov.: 33

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.230 AC: 34921 AN: 152102 Hom.: 4155 Cov.: 33 AF XY: 0.231 AC XY: 17146 AN XY: 74356

Gnomad4 AFR AF: 0.214

Gnomad4 AMR AF: 0.223

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.397

Gnomad4 SAS AF: 0.173

Gnomad4 FIN AF: 0.254

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.202

Alfa AF: 0.224 Hom.: 6245

Bravo AF: 0.230

Asia WGS AF: 0.277 AC: 961 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.24
DANN	Benign	0.35

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: rs3735866; hg19: chr8-1820656;