8-1843472-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014629.4(ARHGEF10):c.37+36T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.536 in 1,536,610 control chromosomes in the GnomAD database, including 227,283 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.45 (17131 hom., cov: 32)
  • Exomes 𝑓: 0.55 (210152 hom.)
• Consequence: ARHGEF10 NM_014629.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.428

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 8-1843472-T-G is Benign according to our data. Variant chr8-1843472-T-G is described in ClinVar as [Benign]. Clinvar id is 1292938.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGEF10	NM_014629.4	c.37+36T>G		intron_variant		ENST00000349830.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGEF10	ENST00000349830.8	c.37+36T>G		intron_variant		1	NM_014629.4	P4
ARHGEF10	ENST00000518288.5	c.109+36T>G		intron_variant		1
ARHGEF10	ENST00000520359.5	c.37+36T>G		intron_variant		1		A2
ARHGEF10	ENST00000398564.5	c.109+36T>G		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68541 AN: 151850 Hom.: 17131 Cov.: 32

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.661

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.547

Gnomad MID AF: 0.400

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.440

GnomAD3 exomes AF: 0.482 AC: 116069 AN: 240852 Hom.: 29248 AF XY: 0.488 AC XY: 63714 AN XY: 130436

Gnomad AFR exome AF: 0.235

Gnomad AMR exome AF: 0.381

Gnomad ASJ exome AF: 0.461

Gnomad EAS exome AF: 0.389

Gnomad SAS exome AF: 0.450

Gnomad FIN exome AF: 0.570

Gnomad NFE exome AF: 0.558

Gnomad OTH exome AF: 0.487

GnomAD4 exome AF: 0.545 AC: 754845 AN: 1384640 Hom.: 210152 Cov.: 22 AF XY: 0.542 AC XY: 375524 AN XY: 692858

Gnomad4 AFR exome AF: 0.232

Gnomad4 AMR exome AF: 0.382

Gnomad4 ASJ exome AF: 0.465

Gnomad4 EAS exome AF: 0.433

Gnomad4 SAS exome AF: 0.447

Gnomad4 FIN exome AF: 0.579

Gnomad4 NFE exome AF: 0.576

Gnomad4 OTH exome AF: 0.515

GnomAD4 genome AF: 0.451 AC: 68563 AN: 151970 Hom.: 17131 Cov.: 32 AF XY: 0.450 AC XY: 33412 AN XY: 74274

Gnomad4 AFR AF: 0.248

Gnomad4 AMR AF: 0.405

Gnomad4 ASJ AF: 0.456

Gnomad4 EAS AF: 0.410

Gnomad4 SAS AF: 0.467

Gnomad4 FIN AF: 0.547

Gnomad4 NFE AF: 0.570

Gnomad4 OTH AF: 0.444

Alfa AF: 0.506 Hom.: 3785

Bravo AF: 0.427

Asia WGS AF: 0.467 AC: 1624 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	5.2
Dann	Benign	0.52

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: rs11136432; hg19: chr8-1791638; COSMIC: COSV50667441;