NM_014629.4:c.38-82_38-81insTATCTATCTATCTATC

Variant names:

• chr8-1857875-G-GATCTATCTATCTATCT
• rs35711467
• NM_014629.4:c.38-82_38-81insTATCTATCTATCTATC

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_014629.4(ARHGEF10):​c.38-82_38-81insTATCTATCTATCTATC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000151 in 918,528 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00028 (0 hom., cov: 21)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: ARHGEF10 NM_014629.4 intron
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 30 Unknown,AD gene.

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

Frequencies

GnomAD3 genomes AF: 0.000280 AC: 30 AN: 107328 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.000163

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000858

Gnomad SAS AF: 0.000294

Gnomad FIN AF: 0.000326

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000369

Gnomad OTH AF: 0.000678

GnomAD4 exome AF: 0.000134 AC: 109 AN: 811114 Hom.: 0 AF XY: 0.000139 AC XY: 58 AN XY: 418256

African (AFR) AF: 0.0000990 AC: 2 AN: 20208

American (AMR) AF: 0.0000615 AC: 2 AN: 32522

Ashkenazi Jewish (ASJ) AF: 0.0000497 AC: 1 AN: 20104

East Asian (EAS) AF: 0.000277 AC: 9 AN: 32448

South Asian (SAS) AF: 0.0000653 AC: 4 AN: 61300

European-Finnish (FIN) AF: 0.000330 AC: 15 AN: 45518

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

European-Non Finnish (NFE) AF: 0.000127 AC: 71 AN: 557016

Other (OTH) AF: 0.000131 AC: 5 AN: 38182

GnomAD4 genome AF: 0.000279 AC: 30 AN: 107414 Hom.: 0 Cov.: 21 AF XY: 0.000250 AC XY: 13 AN XY: 51922

African (AFR) AF: 0.000162 AC: 5 AN: 30818

American (AMR) AF: 0.00 AC: 0 AN: 10232

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2290

East Asian (EAS) AF: 0.000860 AC: 3 AN: 3490

South Asian (SAS) AF: 0.000294 AC: 1 AN: 3406

European-Finnish (FIN) AF: 0.000326 AC: 2 AN: 6132

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 204

European-Non Finnish (NFE) AF: 0.000369 AC: 18 AN: 48752

Other (OTH) AF: 0.000674 AC: 1 AN: 1484

Alfa AF: 0.00 Hom.: 0

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;