rs879696923

Variant names:

• chr4-85570360-CTTTCTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTT-C
• rs879696923
• NM_001025616.3:c.-20-160_-20-125delTTCTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001025616.3(ARHGAP24):​c.-20-160_-20-125delTTCTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTT 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 0.0085 (17 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 4-85570360-CTTTCTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTT-C is Benign according to our data. Variant chr4-85570360-CTTTCTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTT-C is described in ClinVar as [Likely_benign]. Clinvar id is 1800575.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00847 (1115/131604) while in subpopulation AFR AF = 0.0279 (1011/36190). AF 95% confidence interval is 0.0265. There are 17 homozygotes in GnomAd4. There are 504 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1115 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP24	NM_001025616.3	c.-20-160_-20-125delTTCTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTT		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.-20-160_-20-125delTTCTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTT		intron_variant	Intron 1 of 9	2	NM_001025616.3	ENSP00000378611.1

Frequencies

GnomAD3 genomes AF: 0.00845 AC: 1112 AN: 131524 Hom.: 17 Cov.: 0

Gnomad AFR AF: 0.0279

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00217

Gnomad ASJ AF: 0.0125

Gnomad EAS AF: 0.000212

Gnomad SAS AF: 0.000515

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00365

Gnomad NFE AF: 0.000298

Gnomad OTH AF: 0.00913

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

GnomAD4 genome AF: 0.00847 AC: 1115 AN: 131604 Hom.: 17 Cov.: 0 AF XY: 0.00793 AC XY: 504 AN XY: 63582

African (AFR) AF: 0.0279 AC: 1011 AN: 36190

American (AMR) AF: 0.00216 AC: 28 AN: 12942

Ashkenazi Jewish (ASJ) AF: 0.0125 AC: 39 AN: 3128

East Asian (EAS) AF: 0.000213 AC: 1 AN: 4696

South Asian (SAS) AF: 0.000517 AC: 2 AN: 3866

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7570

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 256

European-Non Finnish (NFE) AF: 0.000298 AC: 18 AN: 60370

Other (OTH) AF: 0.00903 AC: 16 AN: 1772

Alfa AF: 0.00573 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 25, 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: rs879696923; hg19: chr4-86491513;