8-1857814-T-C

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.38-146T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0245 in 716,576 control chromosomes in the GnomAD database, including 1,458 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.061 (916 hom., cov: 31)
  • Exomes 𝑓: 0.015 (542 hom.)
• Consequence: ARHGEF10 NM_014629.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.743

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 8-1857814-T-C is Benign according to our data. Variant chr8-1857814-T-C is described in ClinVar as [Benign]. Clinvar id is 1182419.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGEF10	NM_014629.4	c.38-146T>C		intron_variant		ENST00000349830.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGEF10	ENST00000349830.8	c.38-146T>C		intron_variant		1	NM_014629.4	P4
ARHGEF10	ENST00000518288.5	c.110-146T>C		intron_variant		1
ARHGEF10	ENST00000520359.5	c.38-146T>C		intron_variant		1		A2
ARHGEF10	ENST00000398564.5	c.110-146T>C		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.0606 AC: 9202 AN: 151906 Hom.: 913 Cov.: 31

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0214

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.0104

Gnomad FIN AF: 0.00387

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00100

Gnomad OTH AF: 0.0445

GnomAD4 exome AF: 0.0147 AC: 8319 AN: 564552 Hom.: 542 AF XY: 0.0139 AC XY: 4078 AN XY: 293768

Gnomad4 AFR exome AF: 0.189

Gnomad4 AMR exome AF: 0.0121

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.119

Gnomad4 SAS exome AF: 0.0103

Gnomad4 FIN exome AF: 0.00271

Gnomad4 NFE exome AF: 0.000630

Gnomad4 OTH exome AF: 0.0248

GnomAD4 genome AF: 0.0607 AC: 9224 AN: 152024 Hom.: 916 Cov.: 31 AF XY: 0.0598 AC XY: 4444 AN XY: 74328

Gnomad4 AFR AF: 0.192

Gnomad4 AMR AF: 0.0213

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.132

Gnomad4 SAS AF: 0.0108

Gnomad4 FIN AF: 0.00387

Gnomad4 NFE AF: 0.00100

Gnomad4 OTH AF: 0.0450

Alfa AF: 0.0124 Hom.: 132

Bravo AF: 0.0688

Asia WGS AF: 0.0670 AC: 235 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	-1.0
Cadd	Benign	1.3
Dann	Benign	0.43

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: rs17756499; hg19: chr8-1805980;