4-85611279-G-T

Variant names:

• chr4-85611279-G-T
• rs9884932
• NM_001025616.3:c.180+40558G>T

Variant summary

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

The NM_001025616.3(ARHGAP24):​c.180+40558G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 151,940 control chromosomes in the GnomAD database, including 9,352 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 0.33 (9352 hom., cov: 32)
• Consequence: ARHGAP24 NM_001025616.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.273
• Publications: 2 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.82 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP24	NM_001025616.3	MANE Select	c.180+40558G>T		intron	N/A	NP_001020787.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP24	ENST00000395184.6	TSL:2 MANE Select	c.180+40558G>T		intron	N/A	ENSP00000378611.1
	ARHGAP24	ENST00000503995.5	TSL:1	c.180+40558G>T		intron	N/A	ENSP00000423206.1
	ARHGAP24	ENST00000512201.5	TSL:4	c.-171+6976G>T		intron	N/A	ENSP00000426105.1

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50188 AN: 151822 Hom.: 9333 Cov.: 32

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.841

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.342

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

GnomAD4 genome AF: 0.331 AC: 50257 AN: 151940 Hom.: 9352 Cov.: 32 AF XY: 0.340 AC XY: 25286 AN XY: 74272

African (AFR) AF: 0.295 AC: 12236 AN: 41418

American (AMR) AF: 0.441 AC: 6729 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 988 AN: 3462

East Asian (EAS) AF: 0.841 AC: 4352 AN: 5176

South Asian (SAS) AF: 0.468 AC: 2247 AN: 4806

European-Finnish (FIN) AF: 0.312 AC: 3292 AN: 10556

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.285 AC: 19342 AN: 67938

Other (OTH) AF: 0.347 AC: 733 AN: 2112

Alfa AF: 0.310 Hom.: 1378

Bravo AF: 0.340

Asia WGS AF: 0.589 AC: 2043 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.48
DANN	Benign	0.25
PhyloP100		-0.27
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: rs9884932; hg19: chr4-86532432; COSMIC: COSV67846080;