rs2255555

Variant names:

• chr10-31826022-A-G
• rs2255555
• NM_018287.7:c.1530+282T>C

Variant summary

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

The NM_018287.7(ARHGAP12):​c.1530+282T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 152,106 control chromosomes in the GnomAD database, including 3,319 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 0.20 (3319 hom., cov: 32)
• Consequence: ARHGAP12 NM_018287.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.349
• Publications: 3 publications found

Genes affected

ARHGAP12 (HGNC:16348): (Rho GTPase activating protein 12) This gene encodes a member of a large family of proteins that activate Rho-type guanosine triphosphate (GTP) metabolizing enzymes. The encoded protein may be involved in suppressing tumor formation by regulating cell invasion and adhesion. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jul 2012]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018287.7. 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
	ARHGAP12	NM_018287.7	MANE Select	c.1530+282T>C		intron	N/A	NP_060757.4
	ARHGAP12	NM_001270695.1		c.1515+282T>C		intron	N/A	NP_001257624.1
	ARHGAP12	NM_001270696.2		c.1440+282T>C		intron	N/A	NP_001257625.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP12	ENST00000344936.7	TSL:1 MANE Select	c.1530+282T>C		intron	N/A	ENSP00000345808.2
	ARHGAP12	ENST00000396144.8	TSL:1	c.1515+282T>C		intron	N/A	ENSP00000379448.4
	ARHGAP12	ENST00000375250.9	TSL:1	c.1440+282T>C		intron	N/A	ENSP00000364399.5

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30179 AN: 151988 Hom.: 3310 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.222

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

GnomAD4 genome AF: 0.199 AC: 30215 AN: 152106 Hom.: 3319 Cov.: 32 AF XY: 0.202 AC XY: 14985 AN XY: 74354

African (AFR) AF: 0.117 AC: 4880 AN: 41546

American (AMR) AF: 0.280 AC: 4281 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 822 AN: 3472

East Asian (EAS) AF: 0.383 AC: 1978 AN: 5168

South Asian (SAS) AF: 0.276 AC: 1331 AN: 4822

European-Finnish (FIN) AF: 0.163 AC: 1729 AN: 10590

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.212 AC: 14427 AN: 67910

Other (OTH) AF: 0.224 AC: 471 AN: 2106

Alfa AF: 0.211 Hom.: 14947

Bravo AF: 0.202

Asia WGS AF: 0.323 AC: 1125 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.6
DANN	Benign	0.66
PhyloP100		0.35
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: rs2255555; hg19: chr10-32114950;