NM_001025616.3:c.599+13248C>T

Variant names:

• chr4-85955521-C-T
• rs346482
• NM_001025616.3:c.599+13248C>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.599+13248C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.595 in 152,008 control chromosomes in the GnomAD database, including 27,275 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 0.59 (27275 hom., cov: 32)
• Consequence: ARHGAP24 NM_001025616.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.870
• 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.787 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP24	NM_001025616.3	c.599+13248C>T		intron_variant	Intron 5 of 9	ENST00000395184.6	NP_001020787.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP24	ENST00000395184.6	c.599+13248C>T		intron_variant	Intron 5 of 9	2	NM_001025616.3	ENSP00000378611.1

Frequencies

GnomAD3 genomes AF: 0.595 AC: 90299 AN: 151890 Hom.: 27238 Cov.: 32

Gnomad AFR AF: 0.621

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.673

Gnomad ASJ AF: 0.567

Gnomad EAS AF: 0.808

Gnomad SAS AF: 0.714

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.551

Gnomad OTH AF: 0.612

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

GnomAD4 genome AF: 0.595 AC: 90397 AN: 152008 Hom.: 27275 Cov.: 32 AF XY: 0.599 AC XY: 44516 AN XY: 74276

African (AFR) AF: 0.622 AC: 25774 AN: 41460

American (AMR) AF: 0.674 AC: 10283 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.567 AC: 1970 AN: 3472

East Asian (EAS) AF: 0.807 AC: 4172 AN: 5168

South Asian (SAS) AF: 0.715 AC: 3448 AN: 4824

European-Finnish (FIN) AF: 0.506 AC: 5334 AN: 10548

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.551 AC: 37462 AN: 67960

Other (OTH) AF: 0.616 AC: 1300 AN: 2110

Alfa AF: 0.579 Hom.: 5087

Bravo AF: 0.610

Asia WGS AF: 0.742 AC: 2579 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.90
DANN	Benign	0.39
PhyloP100		-0.87
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: rs346482; hg19: chr4-86876674;