chr4-85570431-C-CT

Variant names:

• chr4-85570431-C-CT
• rs202209554
• NM_001025616.3:c.-20-80dupT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.25
• Publications: 1 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 -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 VariationId 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.

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.-20-80dupT		intron	N/A	NP_001020787.2	Q8N264-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP24	ENST00000395184.6	TSL:2 MANE Select	c.-20-91_-20-90insT		intron	N/A	ENSP00000378611.1	Q8N264-1
	ARHGAP24	ENST00000503995.5	TSL:1	c.-20-91_-20-90insT		intron	N/A	ENSP00000423206.1	Q8N264-4
	ARHGAP24	ENST00000505856.1	TSL:2	n.75-91_75-90insT		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.307 AC: 40058 AN: 130666 Hom.: 8032 Cov.: 0

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

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

GnomAD4 genome AF: 0.307 AC: 40111 AN: 130718 Hom.: 8056 Cov.: 0 AF XY: 0.326 AC XY: 20029 AN XY: 61512

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: 38 AN: 204

European-Non Finnish (NFE) AF: 0.152 AC: 9411 AN: 61756

Other (OTH) AF: 0.314 AC: 550 AN: 1750

Alfa AF: 0.0197 Hom.: 24

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3
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: rs202209554; hg19: chr4-86491584; COSMIC: COSV67837446; COSMIC: COSV67837446;