rs4875952

chr8-1837098-A-Gchr8-1837098-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.-47-6255A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 152,194 control chromosomes in the GnomAD database, including 22,729 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 0.54 (22729 hom., cov: 34)
• Consequence: ARHGEF10 NM_014629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0410

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGEF10	NM_014629.4	c.-47-6255A>G		intron_variant		ENST00000349830.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGEF10	ENST00000349830.8	c.-47-6255A>G		intron_variant		1	NM_014629.4	P4
ARHGEF10	ENST00000518288.5	c.26-6255A>G		intron_variant		1
ARHGEF10	ENST00000520359.5	c.-47-6255A>G		intron_variant		1		A2
ARHGEF10	ENST00000398564.5	c.26-6255A>G		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.542 AC: 82382 AN: 152074 Hom.: 22694 Cov.: 34

Gnomad AFR AF: 0.467

Gnomad AMI AF: 0.662

Gnomad AMR AF: 0.622

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.699

Gnomad SAS AF: 0.679

Gnomad FIN AF: 0.581

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.545

Gnomad OTH AF: 0.478

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

GnomAD4 genome AF: 0.542 AC: 82476 AN: 152194 Hom.: 22729 Cov.: 34 AF XY: 0.550 AC XY: 40954 AN XY: 74398

Gnomad4 AFR AF: 0.468

Gnomad4 AMR AF: 0.623

Gnomad4 ASJ AF: 0.475

Gnomad4 EAS AF: 0.699

Gnomad4 SAS AF: 0.679

Gnomad4 FIN AF: 0.581

Gnomad4 NFE AF: 0.545

Gnomad4 OTH AF: 0.482

Alfa AF: 0.542 Hom.: 29391

Bravo AF: 0.539

Asia WGS AF: 0.679 AC: 2363 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	1.2
Dann	Benign	0.75

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: rs4875952; hg19: chr8-1785264;