4-85570364-CTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTT-C

Variant names:

• chr4-85570364-CTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTT-C
• rs56272553
• NM_001025616.3:c.-20-139_-20-104delTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001025616.3(ARHGAP24):​c.-20-139_-20-104delTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTC 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.014 (86 hom., cov: 0)
• Consequence: ARHGAP24 NM_001025616.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 4-85570364-CTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTT-C is Benign according to our data. Variant chr4-85570364-CTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTT-C is described in ClinVar as [Likely_benign]. Clinvar id is 1706919.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP24	NM_001025616.3	c.-20-139_-20-104delTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTC		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.-20-139_-20-104delTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTC		intron_variant	Intron 1 of 9	2	NM_001025616.3	ENSP00000378611.1

Frequencies

GnomAD3 genomes AF: 0.0139 AC: 1942 AN: 139998 Hom.: 87 Cov.: 0

Gnomad AFR AF: 0.00588

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00976

Gnomad ASJ AF: 0.00912

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.00602

Gnomad FIN AF: 0.0665

Gnomad MID AF: 0.00327

Gnomad NFE AF: 0.00572

Gnomad OTH AF: 0.0163

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

GnomAD4 genome AF: 0.0138 AC: 1938 AN: 140052 Hom.: 86 Cov.: 0 AF XY: 0.0166 AC XY: 1115 AN XY: 67234

African (AFR) AF: 0.00590 AC: 219 AN: 37130

American (AMR) AF: 0.00975 AC: 134 AN: 13748

Ashkenazi Jewish (ASJ) AF: 0.00912 AC: 31 AN: 3400

East Asian (EAS) AF: 0.125 AC: 599 AN: 4804

South Asian (SAS) AF: 0.00604 AC: 26 AN: 4302

European-Finnish (FIN) AF: 0.0665 AC: 522 AN: 7848

Middle Eastern (MID) AF: 0.00355 AC: 1 AN: 282

European-Non Finnish (NFE) AF: 0.00570 AC: 375 AN: 65732

Other (OTH) AF: 0.0161 AC: 31 AN: 1920

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 22, 2021

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

See Variant Classification Assertion Criteria. -

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;