Genetic Variant ARHGAP24:c.-20-135_-20-133delTTT (chr4-85570386-CTTT-C) – 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.-20-135_-20-133delTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 33,852 control chromosomes in the GnomAD database, including 6,252 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.17 ( 102 hom., cov: 0)

Exomes 𝑓: 0.58 ( 6150 hom. )

Consequence

ARHGAP24
NM_001025616.3 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0230

Publications

0 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 4-85570386-CTTT-C is Benign according to our data. Variant chr4-85570386-CTTT-C is described in ClinVar as [Benign]. Clinvar id is 1235243.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP24	NM_001025616.3 link	c.-20-135_-20-133delTTT		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.-20-135_-20-133delTTT		intron_variant	Intron 1 of 9	2	NM_001025616.3	ENSP00000378611.1		Q8N264-1

Frequencies

GnomAD3 genomes

AF:

0.173

AC:

1978

AN:

11416

Hom.:

102

Cov.:

show subpopulations

Gnomad AFR

AF:

0.346

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0811

Gnomad ASJ

AF:

0.0154

Gnomad EAS

AF:

0.0161

Gnomad SAS

AF:

0.0351

Gnomad FIN

AF:

0.00593

Gnomad MID

AF:

0.0556

Gnomad NFE

AF:

0.00278

Gnomad OTH

AF:

0.110

GnomAD4 exome

AF:

0.580

AC:

12991

AN:

22412

Hom.:

6150

AF XY:

0.545

AC XY:

6640

AN XY:

12174

show subpopulations

African (AFR)

AF:

0.846

AC:

1098

AN:

1298

American (AMR)

AF:

0.706

AC:

774

AN:

1096

Ashkenazi Jewish (ASJ)

AF:

0.336

AC:

265

AN:

788

East Asian (EAS)

AF:

0.983

AC:

5225

AN:

5318

South Asian (SAS)

AF:

0.304

AC:

630

AN:

2070

European-Finnish (FIN)

AF:

0.402

AC:

345

AN:

858

Middle Eastern (MID)

AF:

0.103

AC:

AN:

564

European-Non Finnish (NFE)

AF:

0.415

AC:

3865

AN:

9316

Other (OTH)

AF:

0.662

AC:

731

AN:

1104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.582

Heterozygous variant carriers

124

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.173

AC:

1982

AN:

11440

Hom.:

102

Cov.:

AF XY:

0.155

AC XY:

898

AN XY:

5780

show subpopulations

African (AFR)

AF:

0.346

AC:

1845

AN:

5334

American (AMR)

AF:

0.0811

AC:

AN:

1196

Ashkenazi Jewish (ASJ)

AF:

0.0154

AC:

AN:

130

East Asian (EAS)

AF:

0.0161

AC:

AN:

124

South Asian (SAS)

AF:

0.0328

AC:

AN:

122

European-Finnish (FIN)

AF:

0.00593

AC:

AN:

674

Middle Eastern (MID)

AF:

0.0625

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00278

AC:

AN:

3596

Other (OTH)

AF:

0.109

AC:

AN:

156

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.544

Heterozygous variant carriers

148

221

295

369

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 15, 2020

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

0.023

Mutation Taster

=100/0

polymorphism

(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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chr4-85570386-CTTT-C

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