8-1955991-T-C

Position:

• chr8-1955991-T-C

Variant summary

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

The ENST00000349830.8(ARHGEF10):​c.3521-758T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 152,134 control chromosomes in the GnomAD database, including 10,073 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 0.36 (10073 hom., cov: 33)
• Consequence: ARHGEF10 ENST00000349830.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0510

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF10	NM_014629.4	c.3521-758T>C		intron_variant		ENST00000349830.8	NP_055444.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGEF10	ENST00000349830.8	c.3521-758T>C		intron_variant		1	NM_014629.4	ENSP00000340297	P4

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54069 AN: 152016 Hom.: 10071 Cov.: 33

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.556

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.376

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

GnomAD4 genome AF: 0.356 AC: 54084 AN: 152134 Hom.: 10073 Cov.: 33 AF XY: 0.359 AC XY: 26672 AN XY: 74346

Gnomad4 AFR AF: 0.264

Gnomad4 AMR AF: 0.306

Gnomad4 ASJ AF: 0.366

Gnomad4 EAS AF: 0.555

Gnomad4 SAS AF: 0.441

Gnomad4 FIN AF: 0.413

Gnomad4 NFE AF: 0.390

Gnomad4 OTH AF: 0.381

Alfa AF: 0.378 Hom.: 14492

Bravo AF: 0.346

Asia WGS AF: 0.515 AC: 1794 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.8
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs4876268; hg19: chr8-1904157;