Genetic Variant ARHGAP12:c.2263+116T>A (chr10-31808878-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.23

Publications

2 publications found

Variant links:

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]

ARHGAP12 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ARHGAP12	NM_018287.7	MANE Select	c.2263+116T>A	intron	N/A	NP_060757.4
ARHGAP12	NM_001270695.1		c.2248+116T>A	intron	N/A	NP_001257624.1
ARHGAP12	NM_001270696.2		c.2173+116T>A	intron	N/A	NP_001257625.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ARHGAP12	ENST00000344936.7	TSL:1 MANE Select	c.2263+116T>A	intron	N/A	ENSP00000345808.2
ARHGAP12	ENST00000396144.8	TSL:1	c.2248+116T>A	intron	N/A	ENSP00000379448.4
ARHGAP12	ENST00000375250.9	TSL:1	c.2173+116T>A	intron	N/A	ENSP00000364399.5

Frequencies

GnomAD3 genomes

AF:

0.198

AC:

30141

AN:

152112

Hom.:

3322

Cov.:

show subpopulations

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.:

AF XY:

0.218

AC XY:

132689

AN XY:

607856

show subpopulations

African (AFR)

AF:

0.112

AC:

3055

AN:

27320

American (AMR)

AF:

0.271

AC:

8784

AN:

32430

Ashkenazi Jewish (ASJ)

AF:

0.233

AC:

4822

AN:

20672

East Asian (EAS)

AF:

0.343

AC:

13058

AN:

38016

South Asian (SAS)

AF:

0.260

AC:

18113

AN:

69730

European-Finnish (FIN)

AF:

0.155

AC:

7621

AN:

49168

Middle Eastern (MID)

AF:

0.241

AC:

1193

AN:

4944

European-Non Finnish (NFE)

AF:

0.212

AC:

195606

AN:

922364

Other (OTH)

AF:

0.224

AC:

11500

AN:

51318

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

10453

20905

31358

41810

52263

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6644

13288

19932

26576

33220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.198

AC:

30176

AN:

152230

Hom.:

3331

Cov.:

AF XY:

0.201

AC XY:

14979

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.115

AC:

4770

AN:

41548

American (AMR)

AF:

0.280

AC:

4279

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.237

AC:

823

AN:

3472

East Asian (EAS)

AF:

0.384

AC:

1989

AN:

5182

South Asian (SAS)

AF:

0.276

AC:

1330

AN:

4824

European-Finnish (FIN)

AF:

0.163

AC:

1733

AN:

10604

Middle Eastern (MID)

AF:

0.218

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.213

AC:

14488

AN:

68006

Other (OTH)

AF:

0.222

AC:

468

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1257

2514

3771

5028

6285

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

326

652

978

1304

1630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

8.5

(source)

DANN

Benign

0.75

PhyloP100

3.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over