8-1843506-C-T

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+70C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 1,227,974 control chromosomes in the GnomAD database, including 144,564 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.42 (13954 hom., cov: 32)
  • Exomes 𝑓: 0.49 (130610 hom.)
• Consequence: ARHGEF10 NM_014629.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.464

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=-0.97).
• BP6: Variant 8-1843506-C-T is Benign according to our data. Variant chr8-1843506-C-T is described in ClinVar as [Benign]. Clinvar id is 1279597.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGEF10	NM_014629.4	c.37+70C>T		intron_variant		ENST00000349830.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGEF10	ENST00000349830.8	c.37+70C>T		intron_variant		1	NM_014629.4	P4
ARHGEF10	ENST00000518288.5	c.109+70C>T		intron_variant		1
ARHGEF10	ENST00000520359.5	c.37+70C>T		intron_variant		1		A2
ARHGEF10	ENST00000398564.5	c.109+70C>T		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63223 AN: 151640 Hom.: 13952 Cov.: 32

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.636

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.500

Gnomad OTH AF: 0.387

GnomAD4 exome AF: 0.491 AC: 528126 AN: 1076216 Hom.: 130610 AF XY: 0.487 AC XY: 267683 AN XY: 549806

Gnomad4 AFR exome AF: 0.287

Gnomad4 AMR exome AF: 0.336

Gnomad4 ASJ exome AF: 0.396

Gnomad4 EAS exome AF: 0.424

Gnomad4 SAS exome AF: 0.431

Gnomad4 FIN exome AF: 0.523

Gnomad4 NFE exome AF: 0.517

Gnomad4 OTH exome AF: 0.465

GnomAD4 genome AF: 0.417 AC: 63249 AN: 151758 Hom.: 13954 Cov.: 32 AF XY: 0.415 AC XY: 30814 AN XY: 74184

Gnomad4 AFR AF: 0.288

Gnomad4 AMR AF: 0.347

Gnomad4 ASJ AF: 0.388

Gnomad4 EAS AF: 0.395

Gnomad4 SAS AF: 0.444

Gnomad4 FIN AF: 0.484

Gnomad4 NFE AF: 0.500

Gnomad4 OTH AF: 0.392

Alfa AF: 0.464 Hom.: 2105

Bravo AF: 0.397

Asia WGS AF: 0.450 AC: 1565 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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	1.4
Dann	Benign	0.33

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: rs11136434; hg19: chr8-1791672; COSMIC: COSV50669899;