8-1872490-G-T

Variant names:

• chr8-1872490-G-T
• rs3735866
• NM_014629.4:c.679+3240G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014629.4(ARHGEF10):​c.679+3240G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 152,102 control chromosomes in the GnomAD database, including 4,155 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 0.23 (4155 hom., cov: 33)
• Consequence: ARHGEF10 NM_014629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 7 publications found

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]

ARHGEF10 Gene-Disease associations (from GenCC):

• autosomal dominant slowed nerve conduction velocity

  Inheritance: Unknown, AD Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet
• hereditary peripheral neuropathy

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• peripheral neuropathy

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

KBTBD11-OT1 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014629.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF10	NM_014629.4	MANE Select	c.679+3240G>T		intron	N/A	NP_055444.2
	ARHGEF10	NM_001438091.1		c.682+3240G>T		intron	N/A	NP_001425020.1
	ARHGEF10	NM_001308153.3		c.682+3240G>T		intron	N/A	NP_001295082.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF10	ENST00000349830.8	TSL:1 MANE Select	c.679+3240G>T		intron	N/A	ENSP00000340297.3
	ARHGEF10	ENST00000518288.5	TSL:1	c.754+3240G>T		intron	N/A	ENSP00000431012.1
	ARHGEF10	ENST00000520359.5	TSL:1	c.682+3240G>T		intron	N/A	ENSP00000427909.1

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34866 AN: 151984 Hom.: 4139 Cov.: 33

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.230 AC: 34921 AN: 152102 Hom.: 4155 Cov.: 33 AF XY: 0.231 AC XY: 17146 AN XY: 74356

African (AFR) AF: 0.214 AC: 8880 AN: 41454

American (AMR) AF: 0.223 AC: 3410 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 764 AN: 3470

East Asian (EAS) AF: 0.397 AC: 2049 AN: 5166

South Asian (SAS) AF: 0.173 AC: 833 AN: 4826

European-Finnish (FIN) AF: 0.254 AC: 2686 AN: 10578

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.229 AC: 15579 AN: 68000

Other (OTH) AF: 0.202 AC: 427 AN: 2110

Alfa AF: 0.225 Hom.: 10606

Bravo AF: 0.230

Asia WGS AF: 0.277 AC: 961 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.24
DANN	Benign	0.35
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3735866; hg19: chr8-1820656;