chr2-143275393-G-A

Position:

• chr2-143275393-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
ARHGAP15	NM_018460.4	c.474+24793G>A		intron_variant		ENST00000295095.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP15	ENST00000295095.11	c.474+24793G>A		intron_variant		1	NM_018460.4	P1

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

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.466

Gnomad4 ASJ AF: 0.261

Gnomad4 EAS AF: 0.353

Gnomad4 SAS AF: 0.413

Gnomad4 FIN AF: 0.250

Gnomad4 NFE AF: 0.300

Gnomad4 OTH AF: 0.302

Alfa AF: 0.303 Hom.: 10004

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

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: rs12993643; hg19: chr2-144032962;