Genetic Variant ARHGAP18:c.-212A>G (chr6-129710348-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.-212A>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0774 in 486,954 control chromosomes in the GnomAD database, including 2,015 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 0.069 ( 539 hom., cov: 32)

Exomes 𝑓: 0.081 ( 1476 hom. )

Consequence

ARHGAP18
NM_033515.3 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.395

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=-0.79).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP18	NM_033515.3 link	c.-212A>G		upstream_gene_variant		ENST00000368149.3	NP_277050.2	Q8N392-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP18	ENST00000368149.3 link	c.-212A>G		upstream_gene_variant		1	NM_033515.3	ENSP00000357131.2		Q8N392-1

Frequencies

GnomAD3 genomes

AF:

0.0688

AC:

10469

AN:

152126

Hom.:

538

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0223

Gnomad AMI

AF:

0.0757

Gnomad AMR

AF:

0.0917

Gnomad ASJ

AF:

0.0738

Gnomad EAS

AF:

0.237

Gnomad SAS

AF:

0.122

Gnomad FIN

AF:

0.132

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0658

Gnomad OTH

AF:

0.0579

GnomAD4 exome

AF:

0.0813

AC:

27228

AN:

334710

Hom.:

1476

AF XY:

0.0821

AC XY:

14233

AN XY:

173438

show subpopulations

African (AFR)

AF:

0.0201

AC:

215

AN:

10718

American (AMR)

AF:

0.0722

AC:

1061

AN:

14702

Ashkenazi Jewish (ASJ)

AF:

0.0712

AC:

766

AN:

10760

East Asian (EAS)

AF:

0.195

AC:

5251

AN:

26866

South Asian (SAS)

AF:

0.105

AC:

2744

AN:

26078

European-Finnish (FIN)

AF:

0.123

AC:

2867

AN:

23368

Middle Eastern (MID)

AF:

0.0332

AC:

AN:

1508

European-Non Finnish (NFE)

AF:

0.0637

AC:

12767

AN:

200318

Other (OTH)

AF:

0.0739

AC:

1507

AN:

20392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1116

2233

3349

4466

5582

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

130

260

390

520

650

<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:

0.0687

AC:

10466

AN:

152244

Hom.:

539

Cov.:

AF XY:

0.0758

AC XY:

5639

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.0222

AC:

924

AN:

41570

American (AMR)

AF:

0.0917

AC:

1403

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0738

AC:

256

AN:

3470

East Asian (EAS)

AF:

0.236

AC:

1220

AN:

5162

South Asian (SAS)

AF:

0.121

AC:

584

AN:

4832

European-Finnish (FIN)

AF:

0.132

AC:

1392

AN:

10584

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0658

AC:

4476

AN:

68008

Other (OTH)

AF:

0.0601

AC:

127

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

483

966

1448

1931

2414

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

252

378

504

630

<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:

0.0600

Hom.:

542

Bravo

AF:

0.0622

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

3.0

(source)

DANN

Benign

0.65

PhyloP100

-0.40

PromoterAI

0.034

Neutral

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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