rs202209554

Variant names:

• chr4-85570431-CTT-C
• rs202209554
• NM_001025616.3:c.-20-81_-20-80delTT

Your query was ambiguous. Multiple possible variants found:

• chr4-85570431-CTT-C
• chr4-85570431-CTT-CT
• chr4-85570431-CTT-CTTT
• chr4-85570431-CTT-CTTTT
• chr4-85570431-CTT-CTTTTT
• chr4-85570431-CTT-CTTTTTT
• chr4-85570431-CTT-CTTTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001025616.3(ARHGAP24):​c.-20-81_-20-80delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000102 in 293,424 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00010 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ARHGAP24 NM_001025616.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP24	NM_001025616.3	c.-20-81_-20-80delTT		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.-20-81_-20-80delTT		intron_variant	Intron 1 of 9	2	NM_001025616.3	ENSP00000378611.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 130802 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

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: 0.000102 AC: 30 AN: 293424 Hom.: 0 AF XY: 0.000111 AC XY: 17 AN XY: 153292

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

African (AFR) AF: 0.00 AC: 0 AN: 7290

American (AMR) AF: 0.000199 AC: 2 AN: 10042

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9172

East Asian (EAS) AF: 0.00 AC: 0 AN: 20410

South Asian (SAS) AF: 0.0000569 AC: 1 AN: 17572

European-Finnish (FIN) AF: 0.000145 AC: 3 AN: 20682

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

European-Non Finnish (NFE) AF: 0.000111 AC: 21 AN: 189904

Other (OTH) AF: 0.000127 AC: 2 AN: 15698

⚠️ 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 Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 130802 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 61508

African (AFR) AF: 0.00 AC: 0 AN: 36154

American (AMR) AF: 0.00 AC: 0 AN: 12282

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 4860

South Asian (SAS) AF: 0.00 AC: 0 AN: 4174

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5474

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 220

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 61826

Other (OTH) AF: 0.00 AC: 0 AN: 1732

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3

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: rs202209554; hg19: chr4-86491584;