rs7003839

Variant names:

• chr8-1869148-G-C
• rs7003839
• NM_014629.4:c.623-46G>C

Your query was ambiguous. Multiple possible variants found:

• chr8-1869148-G-C
• chr8-1869148-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014629.4(ARHGEF10):​c.623-46G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 1,550,380 control chromosomes in the GnomAD database, including 39,500 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3316 hom., cov: 33)
  • Exomes 𝑓: 0.22 (36184 hom.)
• Consequence: ARHGEF10 NM_014629.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.965
• Publications: 8 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 8-1869148-G-C is Benign according to our data. Variant chr8-1869148-G-C is described in ClinVar as Benign. ClinVar VariationId is 1235723.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGEF10	NM_014629.4	c.623-46G>C		intron_variant	Intron 6 of 28	ENST00000349830.8	NP_055444.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGEF10	ENST00000349830.8	c.623-46G>C		intron_variant	Intron 6 of 28	1	NM_014629.4	ENSP00000340297.3
KBTBD11-OT1	ENST00000635855.1	n.*577-46G>C		intron_variant	Intron 7 of 29	5		ENSP00000489726.1

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29955 AN: 151962 Hom.: 3309 Cov.: 33

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.361

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.176

GnomAD2 exomes AF: 0.227 AC: 57048 AN: 251270 AF XY: 0.223

Gnomad AFR exome AF: 0.0929

Gnomad AMR exome AF: 0.259

Gnomad ASJ exome AF: 0.216

Gnomad EAS exome AF: 0.356

Gnomad FIN exome AF: 0.256

Gnomad NFE exome AF: 0.229

Gnomad OTH exome AF: 0.220

GnomAD4 exome AF: 0.224 AC: 312532 AN: 1398300 Hom.: 36184 Cov.: 24 AF XY: 0.221 AC XY: 154876 AN XY: 699494

African (AFR) AF: 0.0924 AC: 2996 AN: 32420

American (AMR) AF: 0.252 AC: 11233 AN: 44626

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 5657 AN: 25756

East Asian (EAS) AF: 0.340 AC: 13372 AN: 39298

South Asian (SAS) AF: 0.163 AC: 13868 AN: 85054

European-Finnish (FIN) AF: 0.251 AC: 13380 AN: 53364

Middle Eastern (MID) AF: 0.133 AC: 755 AN: 5680

European-Non Finnish (NFE) AF: 0.227 AC: 238983 AN: 1053788

Other (OTH) AF: 0.211 AC: 12288 AN: 58314

GnomAD4 genome AF: 0.197 AC: 29993 AN: 152080 Hom.: 3316 Cov.: 33 AF XY: 0.199 AC XY: 14768 AN XY: 74338

African (AFR) AF: 0.101 AC: 4206 AN: 41488

American (AMR) AF: 0.213 AC: 3257 AN: 15274

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

East Asian (EAS) AF: 0.361 AC: 1870 AN: 5182

South Asian (SAS) AF: 0.178 AC: 859 AN: 4828

European-Finnish (FIN) AF: 0.247 AC: 2604 AN: 10554

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.232 AC: 15763 AN: 67970

Other (OTH) AF: 0.179 AC: 378 AN: 2112

Alfa AF: 0.219 Hom.: 653

Bravo AF: 0.193

Asia WGS AF: 0.252 AC: 876 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 10, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.16
DANN	Benign	0.33
PhyloP100		-0.96
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: rs7003839; hg19: chr8-1817314; COSMIC: COSV50667880;