Genetic Variant ARHGAP24:c.-20-80dupT (chr4-85570431-C-CT) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001025616.3(ARHGAP24):c.-20-80dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 413,320 control chromosomes in the GnomAD database, including 14,483 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.31 ( 8056 hom., cov: 0)

Exomes 𝑓: 0.26 ( 6427 hom. )

Consequence

ARHGAP24
NM_001025616.3 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.25

Publications

1 publications found

Variant links:

Genes affected

ARHGAP24 (HGNC:25361): (Rho GTPase activating protein 24) This gene encodes a Rho-GTPase activating protein, which is specific for the small GTPase family member Rac. Binding of the encoded protein by filamin A targets it to sites of membrane protrusion, where it antognizes Rac. This results in suppression of lamellae formation and promotion of retraction to regulate cell polarity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

ARHGAP24 Gene-Disease associations (from GenCC):

familial idiopathic steroid-resistant nephrotic syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ARHGAP24 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 4-85570431-C-CT is Benign according to our data. Variant chr4-85570431-C-CT is described in ClinVar as [Benign]. Clinvar id is 1259699.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.771 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP24	NM_001025616.3 link	c.-20-80dupT		intron_variant	Intron 1 of 9	ENST00000395184.6	NP_001020787.2	Q8N264-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP24	ENST00000395184.6 link	c.-20-80dupT		intron_variant	Intron 1 of 9	2	NM_001025616.3	ENSP00000378611.1		Q8N264-1

Frequencies

GnomAD3 genomes

AF:

0.307

AC:

40058

AN:

130666

Hom.:

8032

Cov.:

show subpopulations

Gnomad AFR

AF:

0.472

Gnomad AMI

AF:

0.120

Gnomad AMR

AF:

0.433

Gnomad ASJ

AF:

0.186

Gnomad EAS

AF:

0.792

Gnomad SAS

AF:

0.426

Gnomad FIN

AF:

0.255

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.152

Gnomad OTH

AF:

0.307

GnomAD4 exome

AF:

0.257

AC:

72595

AN:

282602

Hom.:

6427

AF XY:

0.257

AC XY:

37976

AN XY:

147640

show subpopulations

African (AFR)

AF:

0.415

AC:

2971

AN:

7162

American (AMR)

AF:

0.388

AC:

3815

AN:

9832

Ashkenazi Jewish (ASJ)

AF:

0.267

AC:

2334

AN:

8754

East Asian (EAS)

AF:

0.610

AC:

12393

AN:

20306

South Asian (SAS)

AF:

0.262

AC:

4580

AN:

17454

European-Finnish (FIN)

AF:

0.244

AC:

4833

AN:

19782

Middle Eastern (MID)

AF:

0.212

AC:

550

AN:

2596

European-Non Finnish (NFE)

AF:

0.201

AC:

36574

AN:

181630

Other (OTH)

AF:

0.301

AC:

4545

AN:

15086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

1731

3462

5193

6924

8655

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.307

AC:

40111

AN:

130718

Hom.:

8056

Cov.:

AF XY:

0.326

AC XY:

20029

AN XY:

61512

show subpopulations

African (AFR)

AF:

0.472

AC:

17083

AN:

36196

American (AMR)

AF:

0.434

AC:

5335

AN:

12284

Ashkenazi Jewish (ASJ)

AF:

0.186

AC:

594

AN:

3202

East Asian (EAS)

AF:

0.792

AC:

3838

AN:

4846

South Asian (SAS)

AF:

0.425

AC:

1763

AN:

4148

European-Finnish (FIN)

AF:

0.255

AC:

1394

AN:

5460

Middle Eastern (MID)

AF:

0.186

AC:

AN:

204

European-Non Finnish (NFE)

AF:

0.152

AC:

9411

AN:

61756

Other (OTH)

AF:

0.314

AC:

550

AN:

1750

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1161

2322

3484

4645

5806

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0197

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 24, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.3

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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4-85570431-CTT-CTTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over