rs6990129

Variant names:

• chr8-1912229-G-A
• rs6990129
• NM_014629.4:c.2143+2759G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-1912229-G-A
• chr8-1912229-G-C

Variant summary

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

The NM_014629.4(ARHGEF10):​c.2143+2759G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 151,620 control chromosomes in the GnomAD database, including 4,958 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 0.25 (4958 hom., cov: 32)
• Consequence: ARHGEF10 NM_014629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.364 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.2143+2759G>A		intron	N/A	NP_055444.2	O15013-5
	ARHGEF10	NM_001438091.1		c.2146+2759G>A		intron	N/A	NP_001425020.1
	ARHGEF10	NM_001308153.3		c.2143+2759G>A		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.2143+2759G>A		intron	N/A	ENSP00000340297.3	O15013-5
	ARHGEF10	ENST00000518288.5	TSL:1	c.2215+2759G>A		intron	N/A	ENSP00000431012.1	O15013-6
	ARHGEF10	ENST00000520359.5	TSL:1	c.2029+2759G>A		intron	N/A	ENSP00000427909.1	O15013-7

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38275 AN: 151502 Hom.: 4958 Cov.: 32

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.377

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.257

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

GnomAD4 genome AF: 0.252 AC: 38279 AN: 151620 Hom.: 4958 Cov.: 32 AF XY: 0.256 AC XY: 18956 AN XY: 74072

African (AFR) AF: 0.274 AC: 11327 AN: 41312

American (AMR) AF: 0.239 AC: 3646 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 819 AN: 3462

East Asian (EAS) AF: 0.378 AC: 1925 AN: 5094

South Asian (SAS) AF: 0.305 AC: 1463 AN: 4796

European-Finnish (FIN) AF: 0.288 AC: 3042 AN: 10550

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.226 AC: 15310 AN: 67860

Other (OTH) AF: 0.258 AC: 543 AN: 2102

Alfa AF: 0.229 Hom.: 17135

Bravo AF: 0.249

Asia WGS AF: 0.326 AC: 1135 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.8
DANN	Benign	0.67
PhyloP100		0.36
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: rs6990129; hg19: chr8-1860395;