4-85570364-CTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTT-CTCTTTCTTTCTTTCTT

Variant names:

• chr4-85570364-CTCTTTCTTTCTTTCTTTCTTTCTT-C
• rs56272553
• NM_001025616.3:c.-20-127_-20-104delTTTCTTTCTTTCTTTCTTTCTTTC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001025616.3(ARHGAP24):​c.-20-127_-20-104delTTTCTTTCTTTCTTTCTTTCTTTC 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 0.0032 (7 hom., cov: 0)
• 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: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00322 (451/140058) while in subpopulation EAS AF = 0.0352 (169/4802). AF 95% confidence interval is 0.0309. There are 7 homozygotes in GnomAd4. There are 225 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High AC in GnomAd4 at 451 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP24	NM_001025616.3	c.-20-127_-20-104delTTTCTTTCTTTCTTTCTTTCTTTC		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.-20-127_-20-104delTTTCTTTCTTTCTTTCTTTCTTTC		intron_variant	Intron 1 of 9	2	NM_001025616.3	ENSP00000378611.1

Frequencies

GnomAD3 genomes AF: 0.00320 AC: 448 AN: 140004 Hom.: 7 Cov.: 0

Gnomad AFR AF: 0.00424

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00269

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0353

Gnomad SAS AF: 0.000695

Gnomad FIN AF: 0.000127

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000989

Gnomad OTH AF: 0.00787

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

GnomAD4 genome AF: 0.00322 AC: 451 AN: 140058 Hom.: 7 Cov.: 0 AF XY: 0.00335 AC XY: 225 AN XY: 67238

African (AFR) AF: 0.00431 AC: 160 AN: 37132

American (AMR) AF: 0.00269 AC: 37 AN: 13748

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3400

East Asian (EAS) AF: 0.0352 AC: 169 AN: 4802

South Asian (SAS) AF: 0.000930 AC: 4 AN: 4300

European-Finnish (FIN) AF: 0.000127 AC: 1 AN: 7854

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 282

European-Non Finnish (NFE) AF: 0.000989 AC: 65 AN: 65734

Other (OTH) AF: 0.00781 AC: 15 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;