8-1940281-T-C

Position:

• chr8-1940281-T-C

Variant summary

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

The NM_014629.4(ARHGEF10):​c.3223-5200T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,168 control chromosomes in the GnomAD database, including 1,839 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 0.14 (1839 hom., cov: 32)
• Consequence: ARHGEF10 NM_014629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.931

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]

LOC100131395 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGEF10	NM_014629.4	c.3223-5200T>C		intron_variant		ENST00000349830.8
LOC100131395	XR_110093.6	n.2490A>G		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGEF10	ENST00000349830.8	c.3223-5200T>C		intron_variant		1	NM_014629.4	P4

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21770 AN: 152048 Hom.: 1830 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.0956

Gnomad AMR AF: 0.0819

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.143 AC: 21794 AN: 152168 Hom.: 1839 Cov.: 32 AF XY: 0.149 AC XY: 11083 AN XY: 74404

Gnomad4 AFR AF: 0.178

Gnomad4 AMR AF: 0.0818

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.328

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.231

Gnomad4 NFE AF: 0.107

Gnomad4 OTH AF: 0.156

Alfa AF: 0.115 Hom.: 2368

Bravo AF: 0.136

Asia WGS AF: 0.273 AC: 948 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.50
DANN	Benign	0.53

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: rs3824141; hg19: chr8-1888447;