rs10000472

Variant names:

• chr4-85642011-T-A
• rs10000472
• NM_001025616.3:c.180+71290T>A

Your query was ambiguous. Multiple possible variants found:

• chr4-85642011-T-A
• chr4-85642011-T-C
• chr4-85642011-T-G

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+71290T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 152,002 control chromosomes in the GnomAD database, including 9,644 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 0.34 (9644 hom., cov: 32)
• Consequence: ARHGAP24 NM_001025616.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.587
• Publications: 7 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.819 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.180+71290T>A		intron	N/A	NP_001020787.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP24	ENST00000395184.6	TSL:2 MANE Select	c.180+71290T>A		intron	N/A	ENSP00000378611.1
	ARHGAP24	ENST00000503995.5	TSL:1	c.180+71290T>A		intron	N/A	ENSP00000423206.1
	ARHGAP24	ENST00000512201.5	TSL:4	c.-171+37708T>A		intron	N/A	ENSP00000426105.1

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51143 AN: 151884 Hom.: 9625 Cov.: 32

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.840

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.347

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

GnomAD4 genome AF: 0.337 AC: 51214 AN: 152002 Hom.: 9644 Cov.: 32 AF XY: 0.347 AC XY: 25753 AN XY: 74310

African (AFR) AF: 0.319 AC: 13233 AN: 41474

American (AMR) AF: 0.442 AC: 6745 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 990 AN: 3472

East Asian (EAS) AF: 0.840 AC: 4300 AN: 5120

South Asian (SAS) AF: 0.467 AC: 2254 AN: 4824

European-Finnish (FIN) AF: 0.311 AC: 3292 AN: 10580

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.284 AC: 19314 AN: 67964

Other (OTH) AF: 0.353 AC: 744 AN: 2110

Alfa AF: 0.294 Hom.: 947

Bravo AF: 0.348

Asia WGS AF: 0.593 AC: 2060 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.3
DANN	Benign	0.37
PhyloP100		-0.59
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: rs10000472; hg19: chr4-86563164; COSMIC: COSV67846655;