8-1843267-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.-47-86C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 961,384 control chromosomes in the GnomAD database, including 141,958 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.46 (17758 hom., cov: 32)
  • Exomes 𝑓: 0.55 (124200 hom.)
• Consequence: ARHGEF10 NM_014629.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.530

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=-0.91).
• BP6: Variant 8-1843267-C-T is Benign according to our data. Variant chr8-1843267-C-T is described in ClinVar as [Benign]. Clinvar id is 1244753.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGEF10	NM_014629.4	c.-47-86C>T		intron_variant		ENST00000349830.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGEF10	ENST00000349830.8	c.-47-86C>T		intron_variant		1	NM_014629.4	P4
ARHGEF10	ENST00000518288.5	c.26-86C>T		intron_variant		1
ARHGEF10	ENST00000520359.5	c.-47-86C>T		intron_variant		1		A2
ARHGEF10	ENST00000398564.5	c.26-86C>T		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.461 AC: 70022 AN: 151876 Hom.: 17759 Cov.: 32

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.718

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.598

Gnomad FIN AF: 0.561

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.445

GnomAD4 exome AF: 0.548 AC: 443820 AN: 809390 Hom.: 124200 AF XY: 0.551 AC XY: 230251 AN XY: 417842

Gnomad4 AFR exome AF: 0.246

Gnomad4 AMR exome AF: 0.384

Gnomad4 ASJ exome AF: 0.451

Gnomad4 EAS exome AF: 0.491

Gnomad4 SAS exome AF: 0.579

Gnomad4 FIN exome AF: 0.595

Gnomad4 NFE exome AF: 0.573

Gnomad4 OTH exome AF: 0.521

GnomAD4 genome AF: 0.461 AC: 70045 AN: 151994 Hom.: 17758 Cov.: 32 AF XY: 0.463 AC XY: 34369 AN XY: 74300

Gnomad4 AFR AF: 0.251

Gnomad4 AMR AF: 0.400

Gnomad4 ASJ AF: 0.443

Gnomad4 EAS AF: 0.458

Gnomad4 SAS AF: 0.598

Gnomad4 FIN AF: 0.561

Gnomad4 NFE AF: 0.575

Gnomad4 OTH AF: 0.449

Alfa AF: 0.538 Hom.: 34247

Bravo AF: 0.434

Asia WGS AF: 0.539 AC: 1874 AN: 3476

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	-0.91
Cadd	Benign	3.8
Dann	Benign	0.62

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: rs11136431; hg19: chr8-1791433;