10-31808878-A-T

Variant names:

• chr10-31808878-A-T
• rs1029077
• NM_018287.7:c.2263+116T>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018287.7(ARHGAP12):​c.2263+116T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 1,368,192 control chromosomes in the GnomAD database, including 32,916 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 (3331 hom., cov: 33)
  • Exomes 𝑓: 0.22 (29585 hom.)
• Consequence: ARHGAP12 NM_018287.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.23

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP12	NM_018287.7	c.2263+116T>A		intron_variant	Intron 18 of 19	ENST00000344936.7	NP_060757.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP12	ENST00000344936.7	c.2263+116T>A		intron_variant	Intron 18 of 19	1	NM_018287.7	ENSP00000345808.2

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30141 AN: 152112 Hom.: 3322 Cov.: 33

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.384

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.220

GnomAD4 exome AF: 0.217 AC: 263752 AN: 1215962 Hom.: 29585 Cov.: 17 AF XY: 0.218 AC XY: 132689 AN XY: 607856

Gnomad4 AFR exome AF: 0.112

Gnomad4 AMR exome AF: 0.271

Gnomad4 ASJ exome AF: 0.233

Gnomad4 EAS exome AF: 0.343

Gnomad4 SAS exome AF: 0.260

Gnomad4 FIN exome AF: 0.155

Gnomad4 NFE exome AF: 0.212

Gnomad4 OTH exome AF: 0.224

GnomAD4 genome AF: 0.198 AC: 30176 AN: 152230 Hom.: 3331 Cov.: 33 AF XY: 0.201 AC XY: 14979 AN XY: 74438

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.280

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.384

Gnomad4 SAS AF: 0.276

Gnomad4 FIN AF: 0.163

Gnomad4 NFE AF: 0.213

Gnomad4 OTH AF: 0.222

Alfa AF: 0.0896 Hom.: 126

Bravo AF: 0.201

Asia WGS AF: 0.324 AC: 1127 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.5
DANN	Benign	0.75

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: rs1029077; hg19: chr10-32097806;