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

Variant names:

• chr8-1857875-G-GATCTATCT
• rs35711467
• NM_014629.4:c.38-82_38-81insTATCTATC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_014629.4(ARHGEF10):​c.38-82_38-81insTATCTATC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0181 in 917,620 control chromosomes in the GnomAD database, including 170 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.030 (51 hom., cov: 21)
  • Exomes 𝑓: 0.016 (119 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: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0302 (3247/107350) while in subpopulation EAS AF = 0.0422 (147/3486). AF 95% confidence interval is 0.0366. There are 51 homozygotes in GnomAd4. There are 1573 alleles in the male GnomAd4 subpopulation. Median coverage is 21. This position passed quality control check.
• BS2: High AC in GnomAd4 at 3247 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_38-81insTATCTATC		intron	N/A	NP_055444.2	O15013-5
	ARHGEF10	NM_001438091.1		c.38-82_38-81insTATCTATC		intron	N/A	NP_001425020.1
	ARHGEF10	NM_001308153.3		c.38-82_38-81insTATCTATC		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_38-84insATCTATCT		intron	N/A	ENSP00000340297.3	O15013-5
	ARHGEF10	ENST00000518288.5	TSL:1	c.110-85_110-84insATCTATCT		intron	N/A	ENSP00000431012.1	O15013-6
	ARHGEF10	ENST00000520359.5	TSL:1	c.38-85_38-84insATCTATCT		intron	N/A	ENSP00000427909.1	O15013-7

Frequencies

GnomAD3 genomes AF: 0.0303 AC: 3246 AN: 107262 Hom.: 50 Cov.: 21

Gnomad AFR AF: 0.0235

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0216

Gnomad ASJ AF: 0.0314

Gnomad EAS AF: 0.0421

Gnomad SAS AF: 0.0380

Gnomad FIN AF: 0.0290

Gnomad MID AF: 0.0180

Gnomad NFE AF: 0.0357

Gnomad OTH AF: 0.0210

GnomAD4 exome AF: 0.0165 AC: 13332 AN: 810270 Hom.: 119 AF XY: 0.0171 AC XY: 7150 AN XY: 417828

African (AFR) AF: 0.0127 AC: 257 AN: 20194

American (AMR) AF: 0.0138 AC: 449 AN: 32502

Ashkenazi Jewish (ASJ) AF: 0.0154 AC: 310 AN: 20078

East Asian (EAS) AF: 0.0347 AC: 1126 AN: 32404

South Asian (SAS) AF: 0.0245 AC: 1498 AN: 61242

European-Finnish (FIN) AF: 0.0168 AC: 765 AN: 45468

Middle Eastern (MID) AF: 0.00814 AC: 31 AN: 3810

European-Non Finnish (NFE) AF: 0.0148 AC: 8240 AN: 556424

Other (OTH) AF: 0.0172 AC: 656 AN: 38148

GnomAD4 genome AF: 0.0302 AC: 3247 AN: 107350 Hom.: 51 Cov.: 21 AF XY: 0.0303 AC XY: 1573 AN XY: 51892

African (AFR) AF: 0.0234 AC: 721 AN: 30802

American (AMR) AF: 0.0218 AC: 223 AN: 10222

Ashkenazi Jewish (ASJ) AF: 0.0314 AC: 72 AN: 2290

East Asian (EAS) AF: 0.0422 AC: 147 AN: 3486

South Asian (SAS) AF: 0.0379 AC: 129 AN: 3402

European-Finnish (FIN) AF: 0.0290 AC: 178 AN: 6128

Middle Eastern (MID) AF: 0.0196 AC: 4 AN: 204

European-Non Finnish (NFE) AF: 0.0357 AC: 1741 AN: 48726

Other (OTH) AF: 0.0216 AC: 32 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
Mutation Taster		=100/0	polymorphism

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;