chr8-1920676-G-A

Variant names:

• chr8-1920676-G-A
• rs11136442
• NM_014629.4:c.2144-2288G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014629.4(ARHGEF10):​c.2144-2288G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 152,076 control chromosomes in the GnomAD database, including 31,357 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.63 (31357 hom., cov: 33)
• Consequence: ARHGEF10 NM_014629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0200
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.778 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF10	NM_014629.4	MANE Select	c.2144-2288G>A		intron	N/A	NP_055444.2
	ARHGEF10	NM_001438091.1		c.2147-2288G>A		intron	N/A	NP_001425020.1
	ARHGEF10	NM_001308153.3		c.2144-2288G>A		intron	N/A	NP_001295082.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF10	ENST00000349830.8	TSL:1 MANE Select	c.2144-2288G>A		intron	N/A	ENSP00000340297.3
	ARHGEF10	ENST00000518288.5	TSL:1	c.2216-2288G>A		intron	N/A	ENSP00000431012.1
	ARHGEF10	ENST00000520359.5	TSL:1	c.2030-2288G>A		intron	N/A	ENSP00000427909.1

Frequencies

GnomAD3 genomes AF: 0.633 AC: 96256 AN: 151958 Hom.: 31300 Cov.: 33

Gnomad AFR AF: 0.785

Gnomad AMI AF: 0.598

Gnomad AMR AF: 0.594

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.629

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.590

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.634 AC: 96379 AN: 152076 Hom.: 31357 Cov.: 33 AF XY: 0.634 AC XY: 47160 AN XY: 74342

African (AFR) AF: 0.785 AC: 32601 AN: 41504

American (AMR) AF: 0.594 AC: 9079 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 1740 AN: 3472

East Asian (EAS) AF: 0.488 AC: 2523 AN: 5166

South Asian (SAS) AF: 0.588 AC: 2834 AN: 4816

European-Finnish (FIN) AF: 0.629 AC: 6646 AN: 10560

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.574 AC: 38992 AN: 67962

Other (OTH) AF: 0.592 AC: 1252 AN: 2116

Alfa AF: 0.605 Hom.: 38558

Bravo AF: 0.637

Asia WGS AF: 0.568 AC: 1975 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.62
DANN	Benign	0.47
PhyloP100		-0.020
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs11136442; hg19: chr8-1868842;