chr4-85570364-CTCTTTCTTTCTT-C

Variant names:

• chr4-85570364-CTCTTTCTTTCTT-C
• rs56272553
• NM_001025616.3:c.-20-115_-20-104delTTTCTTTCTTTC

Variant summary

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

The NM_001025616.3(ARHGAP24):​c.-20-115_-20-104delTTTCTTTCTTTC variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0059 (13 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: ARHGAP24 NM_001025616.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.58
• 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.-20-115_-20-104delTTTCTTTCTTTC		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.-20-115_-20-104delTTTCTTTCTTTC		intron_variant	Intron 1 of 9	2	NM_001025616.3	ENSP00000378611.1

Frequencies

GnomAD3 genomes AF: 0.00594 AC: 831 AN: 139978 Hom.: 13 Cov.: 0

Gnomad AFR AF: 0.0210

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00255

Gnomad ASJ AF: 0.000294

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00980

Gnomad NFE AF: 0.0000152

Gnomad OTH AF: 0.00630

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

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00592 AC: 829 AN: 140032 Hom.: 13 Cov.: 0 AF XY: 0.00586 AC XY: 394 AN XY: 67230

African (AFR) AF: 0.0209 AC: 777 AN: 37104

American (AMR) AF: 0.00255 AC: 35 AN: 13742

Ashkenazi Jewish (ASJ) AF: 0.000294 AC: 1 AN: 3400

East Asian (EAS) AF: 0.00 AC: 0 AN: 4806

South Asian (SAS) AF: 0.00 AC: 0 AN: 4302

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7854

Middle Eastern (MID) AF: 0.0106 AC: 3 AN: 282

European-Non Finnish (NFE) AF: 0.0000152 AC: 1 AN: 65736

Other (OTH) AF: 0.00625 AC: 12 AN: 1920

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.6
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs56272553; hg19: chr4-86491517;