rs7007884

Positions:

• chr8-1859590-T-C

Variant summary

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

The NM_014629.4(ARHGEF10):​c.194-307T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 152,100 control chromosomes in the GnomAD database, including 6,811 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 0.30 (6811 hom., cov: 33)
• Consequence: ARHGEF10 NM_014629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.976

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 (SAS) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGEF10	NM_014629.4	c.194-307T>C		intron_variant		ENST00000349830.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGEF10	ENST00000349830.8	c.194-307T>C		intron_variant		1	NM_014629.4	P4

Frequencies

GnomAD3 genomes AF: 0.296 AC: 44945 AN: 151982 Hom.: 6814 Cov.: 33

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.369

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.288

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

GnomAD4 genome AF: 0.296 AC: 44957 AN: 152100 Hom.: 6811 Cov.: 33 AF XY: 0.300 AC XY: 22277 AN XY: 74360

Gnomad4 AFR AF: 0.261

Gnomad4 AMR AF: 0.335

Gnomad4 ASJ AF: 0.233

Gnomad4 EAS AF: 0.301

Gnomad4 SAS AF: 0.441

Gnomad4 FIN AF: 0.284

Gnomad4 NFE AF: 0.301

Gnomad4 OTH AF: 0.291

Alfa AF: 0.301 Hom.: 14037

Bravo AF: 0.293

Asia WGS AF: 0.381 AC: 1329 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	0.27
DANN	Benign	0.43
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs7007884; hg19: chr8-1807756;