rs7826500

Variant names:

• chr8-1893047-T-G
• rs7826500
• NM_014629.4:c.1183-522T>G

Variant summary

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

The NM_014629.4(ARHGEF10):​c.1183-522T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 147,386 control chromosomes in the GnomAD database, including 6,512 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 0.28 (6512 hom., cov: 24)
• Consequence: ARHGEF10 NM_014629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.813
• Publications: 5 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGEF10	NM_014629.4	c.1183-522T>G		intron_variant	Intron 11 of 28	ENST00000349830.8	NP_055444.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGEF10	ENST00000349830.8	c.1183-522T>G		intron_variant	Intron 11 of 28	1	NM_014629.4	ENSP00000340297.3
KBTBD11-OT1	ENST00000635855.1	n.*1137-522T>G		intron_variant	Intron 12 of 29	5		ENSP00000489726.1

Frequencies

GnomAD3 genomes AF: 0.276 AC: 40695 AN: 147288 Hom.: 6503 Cov.: 24

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.306

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.229

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.233

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

GnomAD4 genome AF: 0.276 AC: 40741 AN: 147386 Hom.: 6512 Cov.: 24 AF XY: 0.274 AC XY: 19645 AN XY: 71700

African (AFR) AF: 0.427 AC: 16735 AN: 39194

American (AMR) AF: 0.211 AC: 3117 AN: 14780

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 531 AN: 3456

East Asian (EAS) AF: 0.370 AC: 1846 AN: 4986

South Asian (SAS) AF: 0.348 AC: 1595 AN: 4582

European-Finnish (FIN) AF: 0.166 AC: 1615 AN: 9722

Middle Eastern (MID) AF: 0.231 AC: 67 AN: 290

European-Non Finnish (NFE) AF: 0.215 AC: 14480 AN: 67420

Other (OTH) AF: 0.233 AC: 478 AN: 2052

Alfa AF: 0.243 Hom.: 10763

Bravo AF: 0.287

Asia WGS AF: 0.365 AC: 1265 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.71
DANN	Benign	0.58
PhyloP100		-0.81
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: rs7826500; hg19: chr8-1841213; COSMIC: COSV50653374;