8-1855753-C-T

Variant names:

• chr8-1855753-C-T
• rs9693412
• NM_014629.4:c.38-2207C>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.38-2207C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.669 in 151,912 control chromosomes in the GnomAD database, including 34,227 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 0.67 (34227 hom., cov: 31)
• Consequence: ARHGEF10 NM_014629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47
• 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: AD, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), 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=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.691 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF10	NM_014629.4	MANE Select	c.38-2207C>T		intron	N/A	NP_055444.2	O15013-5
	ARHGEF10	NM_001438091.1		c.38-2207C>T		intron	N/A	NP_001425020.1
	ARHGEF10	NM_001308153.3		c.38-2207C>T		intron	N/A	NP_001295082.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF10	ENST00000349830.8	TSL:1 MANE Select	c.38-2207C>T		intron	N/A	ENSP00000340297.3	O15013-5
	ARHGEF10	ENST00000518288.5	TSL:1	c.110-2207C>T		intron	N/A	ENSP00000431012.1	O15013-6
	ARHGEF10	ENST00000520359.5	TSL:1	c.38-2207C>T		intron	N/A	ENSP00000427909.1	O15013-7

Frequencies

GnomAD3 genomes AF: 0.669 AC: 101588 AN: 151796 Hom.: 34205 Cov.: 31

Gnomad AFR AF: 0.656

Gnomad AMI AF: 0.735

Gnomad AMR AF: 0.654

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.569

Gnomad SAS AF: 0.576

Gnomad FIN AF: 0.696

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.696

Gnomad OTH AF: 0.646

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

GnomAD4 genome AF: 0.669 AC: 101659 AN: 151912 Hom.: 34227 Cov.: 31 AF XY: 0.670 AC XY: 49709 AN XY: 74212

African (AFR) AF: 0.657 AC: 27191 AN: 41416

American (AMR) AF: 0.654 AC: 9981 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.564 AC: 1952 AN: 3462

East Asian (EAS) AF: 0.568 AC: 2936 AN: 5172

South Asian (SAS) AF: 0.574 AC: 2764 AN: 4812

European-Finnish (FIN) AF: 0.696 AC: 7325 AN: 10526

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.696 AC: 47320 AN: 67948

Other (OTH) AF: 0.646 AC: 1357 AN: 2100

Alfa AF: 0.667 Hom.: 16590

Bravo AF: 0.666

Asia WGS AF: 0.591 AC: 2057 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.72
PhyloP100		-1.5
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: rs9693412; hg19: chr8-1803919; COSMIC: COSV50652394; COSMIC: COSV50652394;