rs17829629

Variant names:

• chr8-1869795-C-A
• rs17829629
• ENST00000522969.1:n.1013C>A

Your query was ambiguous. Multiple possible variants found:

• chr8-1869795-C-A
• chr8-1869795-C-G

Variant summary

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

The ENST00000522969.1(ARHGEF10):​n.1013C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 197,506 control chromosomes in the GnomAD database, including 4,818 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 0.22 (3895 hom., cov: 32)
  • Exomes 𝑓: 0.19 (923 hom.)
• Consequence: ARHGEF10 ENST00000522969.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.220
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000522969.1. 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+545C>A		intron	N/A	NP_055444.2
	ARHGEF10	NM_001438091.1		c.682+545C>A		intron	N/A	NP_001425020.1
	ARHGEF10	NM_001308153.3		c.682+545C>A		intron	N/A	NP_001295082.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF10	ENST00000522969.1	TSL:1	n.1013C>A		non_coding_transcript_exon	Exon 4 of 4
	ARHGEF10	ENST00000349830.8	TSL:1 MANE Select	c.679+545C>A		intron	N/A	ENSP00000340297.3
	ARHGEF10	ENST00000518288.5	TSL:1	c.754+545C>A		intron	N/A	ENSP00000431012.1

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33810 AN: 151970 Hom.: 3888 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.338

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.195

GnomAD4 exome AF: 0.189 AC: 8583 AN: 45420 Hom.: 923 Cov.: 0 AF XY: 0.184 AC XY: 4516 AN XY: 24528

African (AFR) AF: 0.148 AC: 159 AN: 1072

American (AMR) AF: 0.235 AC: 799 AN: 3404

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 169 AN: 946

East Asian (EAS) AF: 0.281 AC: 650 AN: 2310

South Asian (SAS) AF: 0.125 AC: 892 AN: 7160

European-Finnish (FIN) AF: 0.190 AC: 308 AN: 1620

Middle Eastern (MID) AF: 0.115 AC: 15 AN: 130

European-Non Finnish (NFE) AF: 0.195 AC: 5209 AN: 26706

Other (OTH) AF: 0.184 AC: 382 AN: 2072

GnomAD4 genome AF: 0.223 AC: 33856 AN: 152086 Hom.: 3895 Cov.: 32 AF XY: 0.223 AC XY: 16595 AN XY: 74340

African (AFR) AF: 0.195 AC: 8078 AN: 41488

American (AMR) AF: 0.218 AC: 3336 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 744 AN: 3464

East Asian (EAS) AF: 0.338 AC: 1749 AN: 5170

South Asian (SAS) AF: 0.168 AC: 811 AN: 4822

European-Finnish (FIN) AF: 0.256 AC: 2713 AN: 10578

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.231 AC: 15706 AN: 67970

Other (OTH) AF: 0.198 AC: 418 AN: 2108

Alfa AF: 0.225 Hom.: 16992

Bravo AF: 0.221

Asia WGS AF: 0.247 AC: 859 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.3
DANN	Benign	0.49
PhyloP100		-0.22
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: rs17829629; hg19: chr8-1817961;