rs4876271

Positions:

• chr8-1953764-G-A

Variant summary

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

The NM_014629.4(ARHGEF10):​c.3520+937G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,196 control chromosomes in the GnomAD database, including 1,440 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 0.14 (1440 hom., cov: 33)
• Consequence: ARHGEF10 NM_014629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.325

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF10	NM_014629.4	c.3520+937G>A		intron_variant		ENST00000349830.8	NP_055444.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGEF10	ENST00000349830.8	c.3520+937G>A		intron_variant		1	NM_014629.4	ENSP00000340297	P4

Frequencies

GnomAD3 genomes AF: 0.138 AC: 21023 AN: 152078 Hom.: 1441 Cov.: 33

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.138 AC: 21030 AN: 152196 Hom.: 1440 Cov.: 33 AF XY: 0.140 AC XY: 10395 AN XY: 74402

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.135

Gnomad4 EAS AF: 0.224

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.143

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.124

Alfa AF: 0.123 Hom.: 1150

Bravo AF: 0.145

Asia WGS AF: 0.163 AC: 564 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.6
DANN	Benign	0.55

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: rs4876271; hg19: chr8-1901930;