rs999545

Positions:

• chr8-1944676-A-G

Variant summary

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

The NM_014629.4(ARHGEF10):​c.3223-805A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 151,982 control chromosomes in the GnomAD database, including 8,481 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 0.32 (8481 hom., cov: 34)
• Consequence: ARHGEF10 NM_014629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0250

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 (AMR) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGEF10	NM_014629.4	c.3223-805A>G		intron_variant		ENST00000349830.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGEF10	ENST00000349830.8	c.3223-805A>G		intron_variant		1	NM_014629.4	P4

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49228 AN: 151864 Hom.: 8475 Cov.: 34

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.312

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

GnomAD4 genome AF: 0.324 AC: 49258 AN: 151982 Hom.: 8481 Cov.: 34 AF XY: 0.325 AC XY: 24138 AN XY: 74266

Gnomad4 AFR AF: 0.225

Gnomad4 AMR AF: 0.411

Gnomad4 ASJ AF: 0.384

Gnomad4 EAS AF: 0.186

Gnomad4 SAS AF: 0.358

Gnomad4 FIN AF: 0.337

Gnomad4 NFE AF: 0.368

Gnomad4 OTH AF: 0.310

Alfa AF: 0.362 Hom.: 5863

Bravo AF: 0.321

Asia WGS AF: 0.235 AC: 816 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	1.2
DANN	Benign	0.45

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: rs999545; hg19: chr8-1892842;