8-1863707-G-T

Variant names:

• chr8-1863707-G-T
• rs13277792
• NM_014629.4:c.482-666G>T

Variant summary

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

The NM_014629.4(ARHGEF10):​c.482-666G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 151,872 control chromosomes in the GnomAD database, including 18,719 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 0.50 (18719 hom., cov: 32)
• Consequence: ARHGEF10 NM_014629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.58
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGEF10	NM_014629.4	c.482-666G>T		intron_variant	Intron 4 of 28	ENST00000349830.8	NP_055444.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGEF10	ENST00000349830.8	c.482-666G>T		intron_variant	Intron 4 of 28	1	NM_014629.4	ENSP00000340297.3
KBTBD11-OT1	ENST00000635855.1	n.*433-663G>T		intron_variant	Intron 5 of 29	5		ENSP00000489726.1

Frequencies

GnomAD3 genomes AF: 0.495 AC: 75157 AN: 151754 Hom.: 18684 Cov.: 32

Gnomad AFR AF: 0.524

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.525

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.478

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

GnomAD4 genome AF: 0.495 AC: 75247 AN: 151872 Hom.: 18719 Cov.: 32 AF XY: 0.495 AC XY: 36736 AN XY: 74178

African (AFR) AF: 0.524 AC: 21721 AN: 41416

American (AMR) AF: 0.436 AC: 6654 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.423 AC: 1467 AN: 3470

East Asian (EAS) AF: 0.488 AC: 2499 AN: 5120

South Asian (SAS) AF: 0.416 AC: 1994 AN: 4796

European-Finnish (FIN) AF: 0.525 AC: 5526 AN: 10532

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.497 AC: 33779 AN: 67950

Other (OTH) AF: 0.482 AC: 1016 AN: 2108

Alfa AF: 0.485 Hom.: 32795

Bravo AF: 0.492

Asia WGS AF: 0.461 AC: 1603 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.12
DANN	Benign	0.47
PhyloP100		-3.6
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: rs13277792; hg19: chr8-1811873;