4-85570364-CTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTT-CTCTTTCTTTCTT

Variant names:

• chr4-85570364-CTCTTTCTTTCTTTCTTTCTTTCTTTCTT-C
• rs56272553
• NM_001025616.3:c.-20-131_-20-104delTTTCTTTCTTTCTTTCTTTCTTTCTTTC

Variant summary

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

The NM_001025616.3(ARHGAP24):​c.-20-131_-20-104delTTTCTTTCTTTCTTTCTTTCTTTCTTTC 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 0.67 (34856 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-CTCTTTCTTTCTTTCTTTCTTTCTTTCTT-C is Benign according to our data. Variant chr4-85570364-CTCTTTCTTTCTTTCTTTCTTTCTTTCTT-C is described in ClinVar as [Benign]. Clinvar id is 1253913.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.842 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP24	NM_001025616.3	c.-20-131_-20-104delTTTCTTTCTTTCTTTCTTTCTTTCTTTC		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.-20-131_-20-104delTTTCTTTCTTTCTTTCTTTCTTTCTTTC		intron_variant	Intron 1 of 9	2	NM_001025616.3	ENSP00000378611.1

Frequencies

GnomAD3 genomes AF: 0.667 AC: 93203 AN: 139788 Hom.: 34865 Cov.: 0

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.871

Gnomad AMR AF: 0.598

Gnomad ASJ AF: 0.814

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.821

Gnomad MID AF: 0.856

Gnomad NFE AF: 0.848

Gnomad OTH AF: 0.681

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

GnomAD4 genome AF: 0.666 AC: 93183 AN: 139842 Hom.: 34856 Cov.: 0 AF XY: 0.658 AC XY: 44164 AN XY: 67130

African (AFR) AF: 0.388 AC: 14362 AN: 37052

American (AMR) AF: 0.597 AC: 8178 AN: 13688

Ashkenazi Jewish (ASJ) AF: 0.814 AC: 2763 AN: 3394

East Asian (EAS) AF: 0.184 AC: 885 AN: 4800

South Asian (SAS) AF: 0.591 AC: 2536 AN: 4294

European-Finnish (FIN) AF: 0.821 AC: 6434 AN: 7836

Middle Eastern (MID) AF: 0.848 AC: 239 AN: 282

European-Non Finnish (NFE) AF: 0.848 AC: 55715 AN: 65692

Other (OTH) AF: 0.677 AC: 1299 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

Jul 24, 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;