8-1857879-GATCTATCTATCTATCTATCTATCTATCTATCT-GATCTATCTATCTATCTATCTATCTATCTATCTATCT

Variant names:

• chr8-1857879-G-GATCT
• rs35698984
• NM_014629.4:c.38-36_38-33dupATCT

Variant summary

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

The NM_014629.4(ARHGEF10):​c.38-36_38-33dupATCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0699 in 593,336 control chromosomes in the GnomAD database, including 930 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.078 (307 hom., cov: 24)
  • Exomes 𝑓: 0.068 (623 hom.)
• Consequence: ARHGEF10 NM_014629.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.397
• 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: 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 -10 ACMG points.

• BP6: Variant 8-1857879-G-GATCT is Benign according to our data. Variant chr8-1857879-G-GATCT is described in ClinVar as Benign. ClinVar VariationId is 1234829.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.141 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.38-36_38-33dupATCT		intron	N/A	NP_055444.2	O15013-5
	ARHGEF10	NM_001438091.1		c.38-36_38-33dupATCT		intron	N/A	NP_001425020.1
	ARHGEF10	NM_001308153.3		c.38-36_38-33dupATCT		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.38-81_38-80insATCT		intron	N/A	ENSP00000340297.3	O15013-5
	ARHGEF10	ENST00000518288.5	TSL:1	c.110-81_110-80insATCT		intron	N/A	ENSP00000431012.1	O15013-6
	ARHGEF10	ENST00000520359.5	TSL:1	c.38-81_38-80insATCT		intron	N/A	ENSP00000427909.1	O15013-7

Frequencies

GnomAD3 genomes AF: 0.0780 AC: 8851 AN: 113496 Hom.: 307 Cov.: 24

Gnomad AFR AF: 0.0859

Gnomad AMI AF: 0.0846

Gnomad AMR AF: 0.0567

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.0469

Gnomad FIN AF: 0.0386

Gnomad MID AF: 0.0856

Gnomad NFE AF: 0.0775

Gnomad OTH AF: 0.0845

GnomAD4 exome AF: 0.0680 AC: 32607 AN: 479768 Hom.: 623 AF XY: 0.0674 AC XY: 17148 AN XY: 254606

African (AFR) AF: 0.0787 AC: 898 AN: 11404

American (AMR) AF: 0.0445 AC: 1015 AN: 22800

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 1444 AN: 13766

East Asian (EAS) AF: 0.132 AC: 3626 AN: 27494

South Asian (SAS) AF: 0.0460 AC: 2093 AN: 45492

European-Finnish (FIN) AF: 0.0343 AC: 1174 AN: 34210

Middle Eastern (MID) AF: 0.0971 AC: 223 AN: 2296

European-Non Finnish (NFE) AF: 0.0675 AC: 20083 AN: 297374

Other (OTH) AF: 0.0823 AC: 2051 AN: 24932

GnomAD4 genome AF: 0.0780 AC: 8862 AN: 113568 Hom.: 307 Cov.: 24 AF XY: 0.0770 AC XY: 4243 AN XY: 55070

African (AFR) AF: 0.0861 AC: 2340 AN: 27184

American (AMR) AF: 0.0565 AC: 639 AN: 11306

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 340 AN: 2694

East Asian (EAS) AF: 0.150 AC: 647 AN: 4308

South Asian (SAS) AF: 0.0471 AC: 171 AN: 3628

European-Finnish (FIN) AF: 0.0386 AC: 287 AN: 7434

Middle Eastern (MID) AF: 0.0905 AC: 19 AN: 210

European-Non Finnish (NFE) AF: 0.0775 AC: 4232 AN: 54580

Other (OTH) AF: 0.0839 AC: 131 AN: 1562

Alfa AF: 0.0157 Hom.: 20

ClinVar

ClinVar submissions as Germline

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		-0.40
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: rs35698984; hg19: chr8-1806045;