rs12993643

Variant names:

• chr2-143275393-G-A
• rs12993643
• NM_018460.4:c.474+24793G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-143275393-G-A
• chr2-143275393-G-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+24793G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 152,098 control chromosomes in the GnomAD database, including 6,507 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 0.27 (6507 hom., cov: 32)
• Consequence: ARHGAP15 NM_018460.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.957
• Publications: 5 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP15	NM_018460.4	c.474+24793G>A		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+24793G>A		intron_variant	Intron 6 of 13	1	NM_018460.4	ENSP00000295095.6

Frequencies

GnomAD3 genomes AF: 0.270 AC: 41075 AN: 151980 Hom.: 6500 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.304

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

GnomAD4 genome AF: 0.270 AC: 41096 AN: 152098 Hom.: 6507 Cov.: 32 AF XY: 0.275 AC XY: 20469 AN XY: 74348

African (AFR) AF: 0.122 AC: 5063 AN: 41520

American (AMR) AF: 0.466 AC: 7103 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 904 AN: 3470

East Asian (EAS) AF: 0.353 AC: 1824 AN: 5172

South Asian (SAS) AF: 0.413 AC: 1990 AN: 4818

European-Finnish (FIN) AF: 0.250 AC: 2642 AN: 10580

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.300 AC: 20425 AN: 67972

Other (OTH) AF: 0.302 AC: 637 AN: 2106

Alfa AF: 0.301 Hom.: 12509

Bravo AF: 0.279

Asia WGS AF: 0.360 AC: 1249 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	0.38
DANN	Benign	0.57
PhyloP100		-0.96
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: rs12993643; hg19: chr2-144032962;