rs2808096

Variant names:

• chr10-31839683-A-G
• rs2808096
• NM_018287.7:c.1325T>C

Your query was ambiguous. Multiple possible variants found:

• chr10-31839683-A-G
• chr10-31839683-A-T

Variant summary

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

The NM_018287.7(ARHGAP12):​c.1325T>C​(p.Phe442Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 1,603,304 control chromosomes in the GnomAD database, including 37,846 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.19 (3151 hom., cov: 32)
  • Exomes 𝑓: 0.21 (34695 hom.)
• Consequence: ARHGAP12 NM_018287.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.05
• Publications: 31 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 (MetaRNN=0.0029663742).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.368 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP12	NM_018287.7	MANE Select	c.1325T>C	p.Phe442Ser	missense	Exon 8 of 20	NP_060757.4
	ARHGAP12	NM_001270695.1		c.1325T>C	p.Phe442Ser	missense	Exon 8 of 19	NP_001257624.1	Q8IWW6-4
	ARHGAP12	NM_001270697.1		c.1184T>C	p.Phe395Ser	missense	Exon 7 of 19	NP_001257626.1	Q1RLN5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP12	ENST00000344936.7	TSL:1 MANE Select	c.1325T>C	p.Phe442Ser	missense	Exon 8 of 20	ENSP00000345808.2	Q8IWW6-1
	ARHGAP12	ENST00000396144.8	TSL:1	c.1325T>C	p.Phe442Ser	missense	Exon 8 of 19	ENSP00000379448.4	Q8IWW6-4
	ARHGAP12	ENST00000375245.8	TSL:1	c.1184T>C	p.Phe395Ser	missense	Exon 7 of 19	ENSP00000364394.5	Q1RLN5

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28548 AN: 151936 Hom.: 3143 Cov.: 32

Gnomad AFR AF: 0.0816

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.210

GnomAD2 exomes AF: 0.221 AC: 55396 AN: 250132 AF XY: 0.223

Gnomad AFR exome AF: 0.0797

Gnomad AMR exome AF: 0.254

Gnomad ASJ exome AF: 0.230

Gnomad EAS exome AF: 0.376

Gnomad FIN exome AF: 0.157

Gnomad NFE exome AF: 0.208

Gnomad OTH exome AF: 0.225

GnomAD4 exome AF: 0.214 AC: 311142 AN: 1451250 Hom.: 34695 Cov.: 31 AF XY: 0.216 AC XY: 155898 AN XY: 722080

African (AFR) AF: 0.0767 AC: 2556 AN: 33316

American (AMR) AF: 0.257 AC: 11428 AN: 44464

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 5994 AN: 25946

East Asian (EAS) AF: 0.344 AC: 13526 AN: 39336

South Asian (SAS) AF: 0.255 AC: 21698 AN: 85180

European-Finnish (FIN) AF: 0.154 AC: 8178 AN: 52970

Middle Eastern (MID) AF: 0.234 AC: 1313 AN: 5616

European-Non Finnish (NFE) AF: 0.211 AC: 233272 AN: 1104496

Other (OTH) AF: 0.220 AC: 13177 AN: 59926

GnomAD4 genome AF: 0.188 AC: 28564 AN: 152054 Hom.: 3151 Cov.: 32 AF XY: 0.191 AC XY: 14212 AN XY: 74334

African (AFR) AF: 0.0815 AC: 3383 AN: 41516

American (AMR) AF: 0.273 AC: 4168 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 823 AN: 3468

East Asian (EAS) AF: 0.382 AC: 1973 AN: 5164

South Asian (SAS) AF: 0.275 AC: 1323 AN: 4814

European-Finnish (FIN) AF: 0.164 AC: 1731 AN: 10568

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

European-Non Finnish (NFE) AF: 0.212 AC: 14420 AN: 67938

Other (OTH) AF: 0.212 AC: 447 AN: 2112

Alfa AF: 0.213 Hom.: 10162

Bravo AF: 0.190

TwinsUK AF: 0.207 AC: 767

ALSPAC AF: 0.210 AC: 810

ESP6500AA AF: 0.0842 AC: 371

ESP6500EA AF: 0.212 AC: 1824

ExAC AF: 0.217 AC: 26400

Asia WGS AF: 0.318 AC: 1108 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.0090	T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.27
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.61	T
MetaRNN	Benign	0.0030	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.46	N
PhyloP100		2.0
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.39	N
REVEL	Benign	0.024
Sift	Benign	0.42	T
Sift4G	Benign	0.41	T
Polyphen		0.0	B
Vest4		0.17
MPC		0.32
ClinPred		0.013	T
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.058
gMVP		0.16
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2808096; hg19: chr10-32128611; COSMIC: COSV60965209;