rs4242549

chr8-1922790-G-Achr8-1922790-G-Cchr8-1922790-G-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.2144-174G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 152,064 control chromosomes in the GnomAD database, including 27,524 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.60 (27524 hom., cov: 33)
• Consequence: ARHGEF10 NM_014629.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.165

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=-0.93).
• BP6: Variant 8-1922790-G-A is Benign according to our data. Variant chr8-1922790-G-A is described in ClinVar as [Benign]. Clinvar id is 1234308.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.875 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGEF10	NM_014629.4	c.2144-174G>A		intron_variant		ENST00000349830.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGEF10	ENST00000349830.8	c.2144-174G>A		intron_variant		1	NM_014629.4	P4

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90712 AN: 151944 Hom.: 27511 Cov.: 33

Gnomad AFR AF: 0.542

Gnomad AMI AF: 0.581

Gnomad AMR AF: 0.655

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.897

Gnomad SAS AF: 0.721

Gnomad FIN AF: 0.662

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.588

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.597 AC: 90756 AN: 152064 Hom.: 27524 Cov.: 33 AF XY: 0.607 AC XY: 45108 AN XY: 74364

Gnomad4 AFR AF: 0.542

Gnomad4 AMR AF: 0.656

Gnomad4 ASJ AF: 0.558

Gnomad4 EAS AF: 0.897

Gnomad4 SAS AF: 0.720

Gnomad4 FIN AF: 0.662

Gnomad4 NFE AF: 0.578

Gnomad4 OTH AF: 0.591

Alfa AF: 0.595 Hom.: 12425

Bravo AF: 0.595

Asia WGS AF: 0.815 AC: 2832 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	-0.93
Cadd	Benign	1.4
Dann	Benign	0.59

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: rs4242549; hg19: chr8-1870956;