chr8-1869795-C-A

Position:

• chr8-1869795-C-A

Variant summary

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

The NM_014629.4(ARHGEF10):​c.679+545C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 197,506 control chromosomes in the GnomAD database, including 4,818 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 0.22 (3895 hom., cov: 32)
  • Exomes 𝑓: 0.19 (923 hom.)
• Consequence: ARHGEF10 NM_014629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.220

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGEF10	NM_014629.4	c.679+545C>A		intron_variant		ENST00000349830.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGEF10	ENST00000349830.8	c.679+545C>A		intron_variant		1	NM_014629.4	P4

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33810 AN: 151970 Hom.: 3888 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.338

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.195

GnomAD4 exome AF: 0.189 AC: 8583 AN: 45420 Hom.: 923 Cov.: 0 AF XY: 0.184 AC XY: 4516 AN XY: 24528

Gnomad4 AFR exome AF: 0.148

Gnomad4 AMR exome AF: 0.235

Gnomad4 ASJ exome AF: 0.179

Gnomad4 EAS exome AF: 0.281

Gnomad4 SAS exome AF: 0.125

Gnomad4 FIN exome AF: 0.190

Gnomad4 NFE exome AF: 0.195

Gnomad4 OTH exome AF: 0.184

GnomAD4 genome AF: 0.223 AC: 33856 AN: 152086 Hom.: 3895 Cov.: 32 AF XY: 0.223 AC XY: 16595 AN XY: 74340

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.218

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.338

Gnomad4 SAS AF: 0.168

Gnomad4 FIN AF: 0.256

Gnomad4 NFE AF: 0.231

Gnomad4 OTH AF: 0.198

Alfa AF: 0.221 Hom.: 7829

Bravo AF: 0.221

Asia WGS AF: 0.247 AC: 859 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.3
DANN	Benign	0.49

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: rs17829629; hg19: chr8-1817961;