rs2255555

Positions:

• chr10-31826022-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP12	NM_018287.7	c.1530+282T>C		intron_variant		ENST00000344936.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP12	ENST00000344936.7	c.1530+282T>C		intron_variant		1	NM_018287.7

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

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.280

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.383

Gnomad4 SAS AF: 0.276

Gnomad4 FIN AF: 0.163

Gnomad4 NFE AF: 0.212

Gnomad4 OTH AF: 0.224

Alfa AF: 0.215 Hom.: 7314

Bravo AF: 0.202

Asia WGS AF: 0.323 AC: 1125 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.6
DANN	Benign	0.66

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: rs2255555; hg19: chr10-32114950;