NM_001025616.3:c.-20-82_-20-80dupTTT

Variant names:

• chr4-85570431-C-CTTT
• rs202209554
• NM_001025616.3:c.-20-82_-20-80dupTTT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001025616.3(ARHGAP24):​c.-20-82_-20-80dupTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000389 in 424,378 control chromosomes in the GnomAD database, including 3 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000038 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00055 (3 hom.)
• Consequence: ARHGAP24 NM_001025616.3 intron
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP24	NM_001025616.3	c.-20-82_-20-80dupTTT		intron_variant	Intron 1 of 9	ENST00000395184.6	NP_001020787.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP24	ENST00000395184.6	c.-20-82_-20-80dupTTT		intron_variant	Intron 1 of 9	2	NM_001025616.3	ENSP00000378611.1

Frequencies

GnomAD3 genomes AF: 0.0000382 AC: 5 AN: 130804 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000138

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000545 AC: 160 AN: 293520 Hom.: 3 AF XY: 0.000548 AC XY: 84 AN XY: 153336

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00371 AC: 27 AN: 7286

American (AMR) AF: 0.00179 AC: 18 AN: 10038

Ashkenazi Jewish (ASJ) AF: 0.000218 AC: 2 AN: 9182

East Asian (EAS) AF: 0.00103 AC: 21 AN: 20346

South Asian (SAS) AF: 0.00131 AC: 23 AN: 17562

European-Finnish (FIN) AF: 0.000435 AC: 9 AN: 20696

Middle Eastern (MID) AF: 0.000377 AC: 1 AN: 2654

European-Non Finnish (NFE) AF: 0.000247 AC: 47 AN: 190044

Other (OTH) AF: 0.000764 AC: 12 AN: 15712

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000382 AC: 5 AN: 130858 Hom.: 0 Cov.: 0 AF XY: 0.0000325 AC XY: 2 AN XY: 61572

African (AFR) AF: 0.000138 AC: 5 AN: 36232

American (AMR) AF: 0.00 AC: 0 AN: 12300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3208

East Asian (EAS) AF: 0.00 AC: 0 AN: 4848

South Asian (SAS) AF: 0.00 AC: 0 AN: 4152

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5476

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 204

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 61814

Other (OTH) AF: 0.00 AC: 0 AN: 1752

Alfa AF: 0.00 Hom.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs202209554; hg19: chr4-86491584;