10-31806321-T-G

Variant names:

• chr10-31806321-T-G
• rs1044795
• ENST00000492028.5:n.2620A>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000492028.5(ARHGAP12):​n.2620A>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 152,512 control chromosomes in the GnomAD database, including 4,730 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 0.24 (4718 hom., cov: 32)
  • Exomes 𝑓: 0.24 (12 hom.)
• Consequence: ARHGAP12 ENST00000492028.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.55
• Publications: 5 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000492028.5. 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.*1337A>C		3_prime_UTR	Exon 20 of 20	NP_060757.4
	ARHGAP12	NM_001270695.1		c.*1337A>C		3_prime_UTR	Exon 19 of 19	NP_001257624.1
	ARHGAP12	NM_001270696.2		c.*1337A>C		3_prime_UTR	Exon 18 of 18	NP_001257625.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP12	ENST00000492028.5	TSL:1	n.2620A>C		non_coding_transcript_exon	Exon 11 of 11
	ARHGAP12	ENST00000497085.1	TSL:1	n.1611A>C		non_coding_transcript_exon	Exon 2 of 2
	ARHGAP12	ENST00000344936.7	TSL:1 MANE Select	c.*1337A>C		3_prime_UTR	Exon 20 of 20	ENSP00000345808.2

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36440 AN: 151982 Hom.: 4712 Cov.: 32

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.233

GnomAD4 exome AF: 0.238 AC: 98 AN: 412 Hom.: 12 Cov.: 0 AF XY: 0.254 AC XY: 63 AN XY: 248

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.239 AC: 97 AN: 406

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.240 AC: 36465 AN: 152100 Hom.: 4718 Cov.: 32 AF XY: 0.243 AC XY: 18040 AN XY: 74354

African (AFR) AF: 0.295 AC: 12228 AN: 41484

American (AMR) AF: 0.228 AC: 3480 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 555 AN: 3470

East Asian (EAS) AF: 0.472 AC: 2450 AN: 5186

South Asian (SAS) AF: 0.232 AC: 1119 AN: 4828

European-Finnish (FIN) AF: 0.228 AC: 2404 AN: 10562

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.199 AC: 13546 AN: 67958

Other (OTH) AF: 0.230 AC: 486 AN: 2112

Alfa AF: 0.209 Hom.: 9480

Bravo AF: 0.243

Asia WGS AF: 0.310 AC: 1075 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	16
DANN	Benign	0.90
PhyloP100		3.5
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: rs1044795; hg19: chr10-32095249;