rs2272712

chr8-1898130-A-G

Variant summary

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

The NM_014629.4(ARHGEF10):c.1558-303A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,078 control chromosomes in the GnomAD database, including 1,573 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 0.12 (1573 hom., cov: 32)
• Consequence: ARHGEF10 NM_014629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.60

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGEF10	NM_014629.4	c.1558-303A>G		intron_variant		ENST00000349830.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGEF10	ENST00000349830.8	c.1558-303A>G		intron_variant		1	NM_014629.4	P4

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18702 AN: 151962 Hom.: 1576 Cov.: 32

Gnomad AFR AF: 0.0303

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.123 AC: 18696 AN: 152078 Hom.: 1573 Cov.: 32 AF XY: 0.124 AC XY: 9250 AN XY: 74348

Gnomad4 AFR AF: 0.0302

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.114

Gnomad4 EAS AF: 0.325

Gnomad4 SAS AF: 0.245

Gnomad4 FIN AF: 0.108

Gnomad4 NFE AF: 0.153

Gnomad4 OTH AF: 0.114

Alfa AF: 0.145 Hom.: 2072

Bravo AF: 0.119

Asia WGS AF: 0.254 AC: 881 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	1.4
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: rs2272712; hg19: chr8-1846296;