dbSNP rs12197456: ARHGAP18:p.Val574Val (chr6-129584104-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_033515.3(ARHGAP18):c.1722T>C(p.Val574Val) variant causes a synonymous change. The variant allele was found at a frequency of 0.0599 in 1,613,446 control chromosomes in the GnomAD database, including 3,219 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 0.048 ( 226 hom., cov: 32)

Exomes 𝑓: 0.061 ( 2993 hom. )

Consequence

ARHGAP18
NM_033515.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.17

Publications

10 publications found

Variant links:

Genes affected

ARHGAP18 (HGNC:21035): (Rho GTPase activating protein 18) Enables GTPase activator activity. Involved in several processes, including regulation of actin filament polymerization; regulation of small GTPase mediated signal transduction; and small GTPase mediated signal transduction. Located in cytosol; nuclear speck; and plasma membrane. Part of cytoplasmic microtubule and ruffle. Implicated in schizophrenia. [provided by Alliance of Genome Resources, Apr 2022]

ARHGAP18 links:

Genome browser will be placed here

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=-0.49).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0635 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP18	NM_033515.3 link	c.1722T>C	p.Val574Val	synonymous_variant	Exon 13 of 15	ENST00000368149.3	NP_277050.2	Q8N392-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ARHGAP18	ENST00000368149.3 link	c.1722T>C	p.Val574Val	synonymous_variant	Exon 13 of 15	1	NM_033515.3	ENSP00000357131.2	Q8N392-1
ARHGAP18	ENST00000463225.1 link	n.100T>C		non_coding_transcript_exon_variant	Exon 2 of 4	3
ARHGAP18	ENST00000483367.5 link	n.96T>C		non_coding_transcript_exon_variant	Exon 2 of 4	3

Frequencies

GnomAD3 genomes

AF:

0.0476

AC:

7239

AN:

152116

Hom.:

226

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0169

Gnomad AMI

AF:

0.0965

Gnomad AMR

AF:

0.0357

Gnomad ASJ

AF:

0.0994

Gnomad EAS

AF:

0.0255

Gnomad SAS

AF:

0.0348

Gnomad FIN

AF:

0.0664

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0651

Gnomad OTH

AF:

0.0541

GnomAD2 exomes

AF:

0.0524

AC:

13135

AN:

250646

AF XY:

0.0531

show subpopulations

Gnomad AFR exome

AF:

0.0170

Gnomad AMR exome

AF:

0.0276

Gnomad ASJ exome

AF:

0.101

Gnomad EAS exome

AF:

0.0235

Gnomad FIN exome

AF:

0.0649

Gnomad NFE exome

AF:

0.0670

Gnomad OTH exome

AF:

0.0642

GnomAD4 exome

AF:

0.0612

AC:

89493

AN:

1461212

Hom.:

2993

Cov.:

AF XY:

0.0608

AC XY:

44208

AN XY:

726884

show subpopulations

African (AFR)

AF:

0.0149

AC:

500

AN:

33452

American (AMR)

AF:

0.0291

AC:

1300

AN:

44678

Ashkenazi Jewish (ASJ)

AF:

0.102

AC:

2669

AN:

26116

East Asian (EAS)

AF:

0.0346

AC:

1372

AN:

39626

South Asian (SAS)

AF:

0.0366

AC:

3158

AN:

86242

European-Finnish (FIN)

AF:

0.0617

AC:

3293

AN:

53368

Middle Eastern (MID)

AF:

0.0504

AC:

290

AN:

5754

European-Non Finnish (NFE)

AF:

0.0659

AC:

73280

AN:

1111610

Other (OTH)

AF:

0.0601

AC:

3631

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

4329

8659

12988

17318

21647

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0475

AC:

7233

AN:

152234

Hom.:

226

Cov.:

AF XY:

0.0466

AC XY:

3467

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.0168

AC:

700

AN:

41550

American (AMR)

AF:

0.0356

AC:

544

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0994

AC:

345

AN:

3470

East Asian (EAS)

AF:

0.0255

AC:

132

AN:

5170

South Asian (SAS)

AF:

0.0346

AC:

167

AN:

4820

European-Finnish (FIN)

AF:

0.0664

AC:

704

AN:

10600

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0651

AC:

4429

AN:

68018

Other (OTH)

AF:

0.0535

AC:

113

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

348

696

1045

1393

1741

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0616

Hom.:

801

Bravo

AF:

0.0451

Asia WGS

AF:

0.0370

AC:

129

AN:

3478

EpiCase

AF:

0.0624

EpiControl

AF:

0.0638

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.80

PhyloP100

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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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rs12197456

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over