rs896656

Variant names:

• chr4-85836983-G-A
• rs896656
• NM_001025616.3:c.269-86665G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001025616.3(ARHGAP24):​c.269-86665G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.668 in 152,038 control chromosomes in the GnomAD database, including 34,245 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 0.67 (34245 hom., cov: 32)
• Consequence: ARHGAP24 NM_001025616.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.665
• Publications: 3 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001025616.3. 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
	ARHGAP24	NM_001025616.3	MANE Select	c.269-86665G>A		intron	N/A	NP_001020787.2	Q8N264-1
	ARHGAP24	NM_001287805.2		c.13+9008G>A		intron	N/A	NP_001274734.1
	ARHGAP24	NM_001042669.2		c.-18+58018G>A		intron	N/A	NP_001036134.1	Q8N264-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP24	ENST00000395184.6	TSL:2 MANE Select	c.269-86665G>A		intron	N/A	ENSP00000378611.1	Q8N264-1
	ARHGAP24	ENST00000395183.6	TSL:1	c.-18+58018G>A		intron	N/A	ENSP00000378610.2	Q8N264-3
	ARHGAP24	ENST00000514229.5	TSL:1	c.13+9008G>A		intron	N/A	ENSP00000425589.1	D6RCP5

Frequencies

GnomAD3 genomes AF: 0.668 AC: 101493 AN: 151922 Hom.: 34233 Cov.: 32

Gnomad AFR AF: 0.603

Gnomad AMI AF: 0.780

Gnomad AMR AF: 0.654

Gnomad ASJ AF: 0.729

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.660

Gnomad FIN AF: 0.653

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.725

Gnomad OTH AF: 0.667

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

GnomAD4 genome AF: 0.668 AC: 101553 AN: 152038 Hom.: 34245 Cov.: 32 AF XY: 0.661 AC XY: 49136 AN XY: 74312

African (AFR) AF: 0.604 AC: 25027 AN: 41468

American (AMR) AF: 0.654 AC: 9987 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.729 AC: 2531 AN: 3470

East Asian (EAS) AF: 0.451 AC: 2325 AN: 5152

South Asian (SAS) AF: 0.658 AC: 3161 AN: 4804

European-Finnish (FIN) AF: 0.653 AC: 6907 AN: 10570

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.725 AC: 49293 AN: 67980

Other (OTH) AF: 0.666 AC: 1405 AN: 2110

Alfa AF: 0.690 Hom.: 4621

Bravo AF: 0.662

Asia WGS AF: 0.566 AC: 1966 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.074
DANN	Benign	0.11
PhyloP100		-0.67
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs896656; hg19: chr4-86758136;