Genetic Variant NM_001025616.3:c.-20-241T>C (chr4-85570281-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001025616.3(ARHGAP24):c.-20-241T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.67 in 151,680 control chromosomes in the GnomAD database, including 37,623 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.67 ( 37623 hom., cov: 28)

Consequence

ARHGAP24
NM_001025616.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0650

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 4-85570281-T-C is Benign according to our data. Variant chr4-85570281-T-C is described in ClinVar as [Benign]. Clinvar id is 1234179.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP24	NM_001025616.3 link	c.-20-241T>C		intron_variant	Intron 1 of 9	ENST00000395184.6	NP_001020787.2	Q8N264-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ARHGAP24	ENST00000395184.6 link	c.-20-241T>C	intron_variant	Intron 1 of 9	2	NM_001025616.3	ENSP00000378611.1	Q8N264-1
ARHGAP24	ENST00000503995.5 link	c.-20-241T>C	intron_variant	Intron 1 of 5	1		ENSP00000423206.1	Q8N264-4
ARHGAP24	ENST00000505856.1 link	n.75-241T>C	intron_variant	Intron 1 of 1	2
ARHGAP24	ENST00000506421.5 link	n.118-241T>C	intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.670

AC:

101589

AN:

151560

Hom.:

37627

Cov.:

show subpopulations

Gnomad AFR

AF:

0.399

Gnomad AMI

AF:

0.884

Gnomad AMR

AF:

0.601

Gnomad ASJ

AF:

0.819

Gnomad EAS

AF:

0.218

Gnomad SAS

AF:

0.599

Gnomad FIN

AF:

0.825

Gnomad MID

AF:

0.856

Gnomad NFE

AF:

0.854

Gnomad OTH

AF:

0.694

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.670

AC:

101592

AN:

151680

Hom.:

37623

Cov.:

AF XY:

0.662

AC XY:

49077

AN XY:

74112

show subpopulations

African (AFR)

AF:

0.398

AC:

16447

AN:

41308

American (AMR)

AF:

0.600

AC:

9149

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.819

AC:

2842

AN:

3472

East Asian (EAS)

AF:

0.218

AC:

1120

AN:

5140

South Asian (SAS)

AF:

0.601

AC:

2881

AN:

4794

European-Finnish (FIN)

AF:

0.825

AC:

8636

AN:

10470

Middle Eastern (MID)

AF:

0.839

AC:

245

AN:

292

European-Non Finnish (NFE)

AF:

0.854

AC:

58017

AN:

67946

Other (OTH)

AF:

0.688

AC:

1449

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1303

2606

3908

5211

6514

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.749

Hom.:

5917

Bravo

AF:

0.638

Asia WGS

AF:

0.443

AC:

1537

AN:

3470

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 11, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.8

(source)

DANN

Benign

0.35

PhyloP100

0.065

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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NM_001025616.3:c.-20-241T>C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over