8-1857875-G-GATCC

Variant names:

• chr8-1857875-G-GATCC
• rs35711467
• NM_014629.4:c.38-82_38-81insCATC

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014629.4(ARHGEF10):​c.38-82_38-81insCATC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000123 in 811,118 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 21)
  • Exomes 𝑓: 0.0000012 (0 hom.)
• Consequence: ARHGEF10 NM_014629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.310
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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_38-81insCATC		intron	N/A	NP_055444.2	O15013-5
	ARHGEF10	NM_001438091.1		c.38-82_38-81insCATC		intron	N/A	NP_001425020.1
	ARHGEF10	NM_001308153.3		c.38-82_38-81insCATC		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_38-84insATCC		intron	N/A	ENSP00000340297.3	O15013-5
	ARHGEF10	ENST00000518288.5	TSL:1	c.110-85_110-84insATCC		intron	N/A	ENSP00000431012.1	O15013-6
	ARHGEF10	ENST00000520359.5	TSL:1	c.38-85_38-84insATCC		intron	N/A	ENSP00000427909.1	O15013-7

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome AF: 0.00000123 AC: 1 AN: 811118 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 418256

African (AFR) AF: 0.00 AC: 0 AN: 20208

American (AMR) AF: 0.00 AC: 0 AN: 32524

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20104

East Asian (EAS) AF: 0.00 AC: 0 AN: 32450

South Asian (SAS) AF: 0.00 AC: 0 AN: 61300

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45518

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3816

European-Non Finnish (NFE) AF: 0.00000180 AC: 1 AN: 557016

Other (OTH) AF: 0.00 AC: 0 AN: 38182

GnomAD4 genome Cov.: 21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.31

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;