rs12640411

Variant names:

• chr4-85648522-C-T
• rs12640411
• NM_001025616.3:c.181-73363C>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.181-73363C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 151,732 control chromosomes in the GnomAD database, including 9,159 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 (9159 hom., cov: 32)
• Consequence: ARHGAP24 NM_001025616.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.139
• Publications: 6 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

LOC105377319 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP24	NM_001025616.3	c.181-73363C>T		intron_variant	Intron 2 of 9	ENST00000395184.6	NP_001020787.2
LOC105377319	XR_007058168.1	n.4006+1012C>T		intron_variant	Intron 1 of 3
LOC105377319	XR_938955.4	n.4006+1012C>T		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP24	ENST00000395184.6	c.181-73363C>T		intron_variant	Intron 2 of 9	2	NM_001025616.3	ENSP00000378611.1

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49370 AN: 151614 Hom.: 9137 Cov.: 32

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.841

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.333

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

GnomAD4 genome AF: 0.326 AC: 49441 AN: 151732 Hom.: 9159 Cov.: 32 AF XY: 0.334 AC XY: 24778 AN XY: 74154

African (AFR) AF: 0.280 AC: 11607 AN: 41394

American (AMR) AF: 0.436 AC: 6614 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 991 AN: 3466

East Asian (EAS) AF: 0.841 AC: 4337 AN: 5154

South Asian (SAS) AF: 0.467 AC: 2249 AN: 4812

European-Finnish (FIN) AF: 0.313 AC: 3293 AN: 10530

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

European-Non Finnish (NFE) AF: 0.284 AC: 19297 AN: 67882

Other (OTH) AF: 0.339 AC: 714 AN: 2106

Alfa AF: 0.309 Hom.: 1449

Bravo AF: 0.336

Asia WGS AF: 0.595 AC: 2067 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.0
DANN	Benign	0.40
PhyloP100		0.14
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: rs12640411; hg19: chr4-86569675;