Genetic Variant ARHGAP18:c.553-77A>G (chr6-129634182-T-C) – 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.553-77A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 1,300,260 control chromosomes in the GnomAD database, including 59,814 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 0.27 ( 5849 hom., cov: 31)

Exomes 𝑓: 0.30 ( 53965 hom. )

Consequence

ARHGAP18
NM_033515.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.297

Publications

9 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:

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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=-0.64).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033515.3. 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
	ARHGAP18	NM_033515.3	MANE Select	c.553-77A>G		intron	N/A	NP_277050.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ARHGAP18	ENST00000368149.3	TSL:1 MANE Select	c.553-77A>G	intron	N/A	ENSP00000357131.2	Q8N392-1
ARHGAP18	ENST00000909755.1		c.553-77A>G	intron	N/A	ENSP00000579814.1
ARHGAP18	ENST00000938085.1		c.553-77A>G	intron	N/A	ENSP00000608144.1

Frequencies

GnomAD3 genomes

AF:

0.267

AC:

40539

AN:

151902

Hom.:

5842

Cov.:

show subpopulations

Gnomad AFR

AF:

0.163

Gnomad AMI

AF:

0.240

Gnomad AMR

AF:

0.279

Gnomad ASJ

AF:

0.294

Gnomad EAS

AF:

0.169

Gnomad SAS

AF:

0.235

Gnomad FIN

AF:

0.334

Gnomad MID

AF:

0.297

Gnomad NFE

AF:

0.325

Gnomad OTH

AF:

0.294

GnomAD4 exome

AF:

0.298

AC:

342281

AN:

1148240

Hom.:

53965

AF XY:

0.297

AC XY:

173195

AN XY:

583564

show subpopulations

African (AFR)

AF:

0.164

AC:

4391

AN:

26732

American (AMR)

AF:

0.222

AC:

8902

AN:

40152

Ashkenazi Jewish (ASJ)

AF:

0.301

AC:

7014

AN:

23340

East Asian (EAS)

AF:

0.166

AC:

6304

AN:

38044

South Asian (SAS)

AF:

0.222

AC:

16943

AN:

76470

European-Finnish (FIN)

AF:

0.349

AC:

17929

AN:

51408

Middle Eastern (MID)

AF:

0.313

AC:

1579

AN:

5048

European-Non Finnish (NFE)

AF:

0.316

AC:

264520

AN:

837240

Other (OTH)

AF:

0.295

AC:

14699

AN:

49806

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

11228

22456

33684

44912

56140

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7384

14768

22152

29536

36920

<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:

0.267

AC:

40570

AN:

152020

Hom.:

5849

Cov.:

AF XY:

0.266

AC XY:

19745

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.163

AC:

6750

AN:

41478

American (AMR)

AF:

0.279

AC:

4258

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.294

AC:

1020

AN:

3470

East Asian (EAS)

AF:

0.169

AC:

876

AN:

5176

South Asian (SAS)

AF:

0.235

AC:

1135

AN:

4824

European-Finnish (FIN)

AF:

0.334

AC:

3525

AN:

10544

Middle Eastern (MID)

AF:

0.286

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.325

AC:

22079

AN:

67946

Other (OTH)

AF:

0.295

AC:

624

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1501

3002

4504

6005

7506

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

420

840

1260

1680

2100

<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:

0.301

Hom.:

14571

Bravo

AF:

0.257

Asia WGS

AF:

0.219

AC:

761

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Benign

0.90

PhyloP100

0.30

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