8-1857875-G-GATCT

Variant names:

• chr8-1857875-G-GATCT
• rs35711467
• NM_014629.4:c.38-82_38-81insTATC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_014629.4(ARHGEF10):​c.38-82_38-81insTATC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0969 in 913,524 control chromosomes in the GnomAD database, including 3,602 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (1185 hom., cov: 21)
  • Exomes 𝑓: 0.087 (2417 hom.)
• Consequence: ARHGEF10 NM_014629.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.310
• Publications: 1 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 -10 ACMG points.

• BP6: Variant 8-1857875-G-GATCT is Benign according to our data. Variant chr8-1857875-G-GATCT is described in ClinVar as Benign. ClinVar VariationId is 1229075.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.209 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.38-82_38-81insTATC		intron	N/A	NP_055444.2	O15013-5
	ARHGEF10	NM_001438091.1		c.38-82_38-81insTATC		intron	N/A	NP_001425020.1
	ARHGEF10	NM_001308153.3		c.38-82_38-81insTATC		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.38-85_38-84insATCT		intron	N/A	ENSP00000340297.3	O15013-5
	ARHGEF10	ENST00000518288.5	TSL:1	c.110-85_110-84insATCT		intron	N/A	ENSP00000431012.1	O15013-6
	ARHGEF10	ENST00000520359.5	TSL:1	c.38-85_38-84insATCT		intron	N/A	ENSP00000427909.1	O15013-7

Frequencies

GnomAD3 genomes AF: 0.172 AC: 18428 AN: 106964 Hom.: 1185 Cov.: 21

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.140

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.141

GnomAD4 exome AF: 0.0869 AC: 70069 AN: 806472 Hom.: 2417 AF XY: 0.0904 AC XY: 37584 AN XY: 415852

African (AFR) AF: 0.0797 AC: 1603 AN: 20110

American (AMR) AF: 0.0941 AC: 3039 AN: 32282

Ashkenazi Jewish (ASJ) AF: 0.0522 AC: 1045 AN: 20026

East Asian (EAS) AF: 0.156 AC: 5030 AN: 32294

South Asian (SAS) AF: 0.138 AC: 8411 AN: 60962

European-Finnish (FIN) AF: 0.123 AC: 5551 AN: 45214

Middle Eastern (MID) AF: 0.0598 AC: 227 AN: 3798

European-Non Finnish (NFE) AF: 0.0752 AC: 41647 AN: 553808

Other (OTH) AF: 0.0926 AC: 3516 AN: 37978

GnomAD4 genome AF: 0.172 AC: 18439 AN: 107052 Hom.: 1185 Cov.: 21 AF XY: 0.174 AC XY: 8989 AN XY: 51758

African (AFR) AF: 0.143 AC: 4385 AN: 30730

American (AMR) AF: 0.160 AC: 1628 AN: 10198

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 230 AN: 2284

East Asian (EAS) AF: 0.201 AC: 697 AN: 3468

South Asian (SAS) AF: 0.222 AC: 751 AN: 3388

European-Finnish (FIN) AF: 0.198 AC: 1209 AN: 6114

Middle Eastern (MID) AF: 0.132 AC: 27 AN: 204

European-Non Finnish (NFE) AF: 0.187 AC: 9107 AN: 48584

Other (OTH) AF: 0.140 AC: 206 AN: 1476

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.31
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs35711467; hg19: chr8-1806041;