rs10503168

Positions:

• chr8-1869120-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014629.4(ARHGEF10):​c.623-74G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0299 in 1,305,164 control chromosomes in the GnomAD database, including 1,226 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.057 (473 hom., cov: 33)
  • Exomes 𝑓: 0.026 (753 hom.)
• Consequence: ARHGEF10 NM_014629.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.75

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 8-1869120-G-T is Benign according to our data. Variant chr8-1869120-G-T is described in ClinVar as [Benign]. Clinvar id is 1279705.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGEF10	NM_014629.4	c.623-74G>T		intron_variant		ENST00000349830.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGEF10	ENST00000349830.8	c.623-74G>T		intron_variant		1	NM_014629.4	P4

Frequencies

GnomAD3 genomes AF: 0.0570 AC: 8664 AN: 152030 Hom.: 467 Cov.: 33

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0288

Gnomad ASJ AF: 0.0144

Gnomad EAS AF: 0.0423

Gnomad SAS AF: 0.00435

Gnomad FIN AF: 0.0452

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0208

Gnomad OTH AF: 0.0503

GnomAD4 exome AF: 0.0263 AC: 30297 AN: 1153016 Hom.: 753 AF XY: 0.0246 AC XY: 14496 AN XY: 589238

Gnomad4 AFR exome AF: 0.152

Gnomad4 AMR exome AF: 0.0200

Gnomad4 ASJ exome AF: 0.0144

Gnomad4 EAS exome AF: 0.0549

Gnomad4 SAS exome AF: 0.00357

Gnomad4 FIN exome AF: 0.0423

Gnomad4 NFE exome AF: 0.0224

Gnomad4 OTH exome AF: 0.0314

GnomAD4 genome AF: 0.0571 AC: 8689 AN: 152148 Hom.: 473 Cov.: 33 AF XY: 0.0571 AC XY: 4249 AN XY: 74356

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.0287

Gnomad4 ASJ AF: 0.0144

Gnomad4 EAS AF: 0.0417

Gnomad4 SAS AF: 0.00373

Gnomad4 FIN AF: 0.0452

Gnomad4 NFE AF: 0.0208

Gnomad4 OTH AF: 0.0498

Alfa AF: 0.0246 Hom.: 118

Bravo AF: 0.0599

Asia WGS AF: 0.0280 AC: 96 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 11, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.011
DANN	Benign	0.77

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: rs10503168; hg19: chr8-1817286;