rs10176394

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018460.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP15	NM_018460.4	MANE Select	c.474+88205T>C		intron	N/A	NP_060930.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP15	ENST00000295095.11	TSL:1 MANE Select	c.474+88205T>C		intron	N/A	ENSP00000295095.6
	ENSG00000228655	ENST00000442794.1	TSL:4	n.400+5239A>G		intron	N/A
	ARHGAP15	ENST00000460776.5	TSL:5	n.422+88205T>C		intron	N/A

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

African (AFR) AF: 0.0907 AC: 3762 AN: 41484

American (AMR) AF: 0.112 AC: 1705 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 394 AN: 3466

East Asian (EAS) AF: 0.00329 AC: 17 AN: 5172

South Asian (SAS) AF: 0.0845 AC: 408 AN: 4828

European-Finnish (FIN) AF: 0.298 AC: 3146 AN: 10570

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.162 AC: 11010 AN: 67962

Other (OTH) AF: 0.129 AC: 272 AN: 2110

Alfa AF: 0.150 Hom.: 278

Bravo AF: 0.124

Asia WGS AF: 0.0670 AC: 235 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	17
DANN	Benign	0.91
PhyloP100		2.3
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: rs10176394; hg19: chr2-144096374;