chr4-85570364-CTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTT-C

Variant names:

• chr4-85570364-CTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTT-C
• rs56272553
• NM_001025616.3:c.-20-135_-20-104delTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTC

Variant summary

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

The NM_001025616.3(ARHGAP24):​c.-20-135_-20-104delTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTC 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 Benign (★).

• Frequency: Genomes: 𝑓 0.28 (7868 hom., cov: 0)
• Consequence: ARHGAP24 NM_001025616.3 intron
• Clinical Significance: 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-CTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTT-C is Benign according to our data. Variant chr4-85570364-CTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTT-C is described in ClinVar as [Benign]. Clinvar id is 1270853.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP24	NM_001025616.3	c.-20-135_-20-104delTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTC		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.-20-135_-20-104delTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTC		intron_variant	Intron 1 of 9	2	NM_001025616.3	ENSP00000378611.1

Frequencies

GnomAD3 genomes AF: 0.279 AC: 39040 AN: 139838 Hom.: 7836 Cov.: 0

Gnomad AFR AF: 0.481

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.648

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.124

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.263

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

GnomAD4 genome AF: 0.280 AC: 39107 AN: 139892 Hom.: 7868 Cov.: 0 AF XY: 0.286 AC XY: 19236 AN XY: 67152

African (AFR) AF: 0.482 AC: 17850 AN: 37054

American (AMR) AF: 0.372 AC: 5097 AN: 13712

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 551 AN: 3400

East Asian (EAS) AF: 0.649 AC: 3118 AN: 4802

South Asian (SAS) AF: 0.390 AC: 1678 AN: 4298

European-Finnish (FIN) AF: 0.105 AC: 822 AN: 7840

Middle Eastern (MID) AF: 0.135 AC: 38 AN: 282

European-Non Finnish (NFE) AF: 0.142 AC: 9330 AN: 65700

Other (OTH) AF: 0.267 AC: 512 AN: 1918

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 18, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

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

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;