rs10176394

Variant names:

• chr2-143338805-T-C
• rs10176394
• NM_018460.4:c.474+88205T>C

Variant summary

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

The NM_018460.4(ARHGAP15):​c.474+88205T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,070 control chromosomes in the GnomAD database, including 1,712 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 (1712 hom., cov: 31)
• Consequence: ARHGAP15 NM_018460.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.32

Genes affected

ARHGAP15 (HGNC:21030): (Rho GTPase activating protein 15) RHO GTPases (see ARHA; MIM 165390) regulate diverse biologic processes, and their activity is regulated by RHO GTPase-activating proteins (GAPs), such as ARHGAP15 (Seoh et al., 2003 [PubMed 12650940]).[supplied by OMIM, Mar 2008]

ENSG00000228655 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP15	NM_018460.4	c.474+88205T>C		intron_variant	Intron 6 of 13	ENST00000295095.11	NP_060930.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP15	ENST00000295095.11	c.474+88205T>C		intron_variant	Intron 6 of 13	1	NM_018460.4	ENSP00000295095.6

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20922 AN: 151952 Hom.: 1707 Cov.: 31

Gnomad AFR AF: 0.0903

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.00328

Gnomad SAS AF: 0.0840

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.130

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

GnomAD4 genome AF: 0.138 AC: 20953 AN: 152070 Hom.: 1712 Cov.: 31 AF XY: 0.141 AC XY: 10483 AN XY: 74356

Gnomad4 AFR AF: 0.0907

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.114

Gnomad4 EAS AF: 0.00329

Gnomad4 SAS AF: 0.0845

Gnomad4 FIN AF: 0.298

Gnomad4 NFE AF: 0.162

Gnomad4 OTH AF: 0.129

Alfa AF: 0.153 Hom.: 278

Bravo AF: 0.124

Asia WGS AF: 0.0670 AC: 235 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	17
DANN	Benign	0.91

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: rs10176394; hg19: chr2-144096374;