NM_018460.4:c.235-6561G>A

Variant names:

• chr2-143209823-G-A
• rs1376749
• NM_018460.4:c.235-6561G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018460.4(ARHGAP15):​c.235-6561G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 152,122 control chromosomes in the GnomAD database, including 2,424 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 0.17 (2424 hom., cov: 32)
• Consequence: ARHGAP15 NM_018460.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.180
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP15	NM_018460.4	c.235-6561G>A		intron_variant	Intron 3 of 13	ENST00000295095.11	NP_060930.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP15	ENST00000295095.11	c.235-6561G>A		intron_variant	Intron 3 of 13	1	NM_018460.4	ENSP00000295095.6
ARHGAP15	ENST00000409869.5	c.235-6561G>A		intron_variant	Intron 4 of 6	5		ENSP00000386560.1
ARHGAP15	ENST00000460776.5	n.183-6561G>A		intron_variant	Intron 2 of 5	5
ARHGAP15	ENST00000552641.5	n.303-6561G>A		intron_variant	Intron 3 of 7	2

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25941 AN: 152004 Hom.: 2416 Cov.: 32

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.250

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.171 AC: 25988 AN: 152122 Hom.: 2424 Cov.: 32 AF XY: 0.171 AC XY: 12717 AN XY: 74384

African (AFR) AF: 0.234 AC: 9706 AN: 41472

American (AMR) AF: 0.185 AC: 2826 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 558 AN: 3472

East Asian (EAS) AF: 0.115 AC: 598 AN: 5178

South Asian (SAS) AF: 0.200 AC: 966 AN: 4824

European-Finnish (FIN) AF: 0.107 AC: 1138 AN: 10598

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.140 AC: 9526 AN: 67990

Other (OTH) AF: 0.175 AC: 370 AN: 2112

Alfa AF: 0.149 Hom.: 961

Bravo AF: 0.178

Asia WGS AF: 0.179 AC: 622 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.6
DANN	Benign	0.66
PhyloP100		0.18
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: rs1376749; hg19: chr2-143967392;