8-1956098-C-T

Position:

• chr8-1956098-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014629.4(ARHGEF10):​c.3521-651C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 152,156 control chromosomes in the GnomAD database, including 7,087 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 0.29 (7087 hom., cov: 33)
• Consequence: ARHGEF10 NM_014629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.30

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]

KBTBD11-OT1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF10	NM_014629.4	c.3521-651C>T		intron_variant		ENST00000349830.8	NP_055444.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGEF10	ENST00000349830.8	c.3521-651C>T		intron_variant		1	NM_014629.4	ENSP00000340297.3
KBTBD11-OT1	ENST00000635855.1	n.*3475-651C>T		intron_variant		5		ENSP00000489726.1

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44806 AN: 152038 Hom.: 7080 Cov.: 33

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.284

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

GnomAD4 genome AF: 0.295 AC: 44831 AN: 152156 Hom.: 7087 Cov.: 33 AF XY: 0.298 AC XY: 22167 AN XY: 74384

Gnomad4 AFR AF: 0.190

Gnomad4 AMR AF: 0.379

Gnomad4 ASJ AF: 0.376

Gnomad4 EAS AF: 0.219

Gnomad4 SAS AF: 0.333

Gnomad4 FIN AF: 0.333

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.282

Alfa AF: 0.325 Hom.: 4293

Bravo AF: 0.291

Asia WGS AF: 0.234 AC: 812 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.26
DANN	Benign	0.70

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

Publications

LitVar

Other links and lift over

dbSNP: rs6999840; hg19: chr8-1904264;