rs11136442

Positions:

• chr8-1920676-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014629.4(ARHGEF10):​c.2144-2288G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 152,076 control chromosomes in the GnomAD database, including 31,357 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.63 (31357 hom., cov: 33)
• Consequence: ARHGEF10 NM_014629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0200

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF10	NM_014629.4	c.2144-2288G>A		intron_variant		ENST00000349830.8	NP_055444.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGEF10	ENST00000349830.8	c.2144-2288G>A		intron_variant		1	NM_014629.4	ENSP00000340297	P4

Frequencies

GnomAD3 genomes AF: 0.633 AC: 96256 AN: 151958 Hom.: 31300 Cov.: 33

Gnomad AFR AF: 0.785

Gnomad AMI AF: 0.598

Gnomad AMR AF: 0.594

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.629

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.590

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

GnomAD4 genome AF: 0.634 AC: 96379 AN: 152076 Hom.: 31357 Cov.: 33 AF XY: 0.634 AC XY: 47160 AN XY: 74342

Gnomad4 AFR AF: 0.785

Gnomad4 AMR AF: 0.594

Gnomad4 ASJ AF: 0.501

Gnomad4 EAS AF: 0.488

Gnomad4 SAS AF: 0.588

Gnomad4 FIN AF: 0.629

Gnomad4 NFE AF: 0.574

Gnomad4 OTH AF: 0.592

Alfa AF: 0.594 Hom.: 22804

Bravo AF: 0.637

Asia WGS AF: 0.568 AC: 1975 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.62
DANN	Benign	0.47

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: rs11136442; hg19: chr8-1868842;