rs7692808

Variant names:

• chr4-85719996-A-G
• rs7692808
• NM_001025616.3:c.181-1889A>G

Your query was ambiguous. Multiple possible variants found:

• chr4-85719996-A-G
• chr4-85719996-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001025616.3(ARHGAP24):​c.181-1889A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 151,762 control chromosomes in the GnomAD database, including 22,961 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.51 (22961 hom., cov: 29)
• Consequence: ARHGAP24 NM_001025616.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0680
• Publications: 25 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP24	NM_001025616.3	c.181-1889A>G		intron_variant	Intron 2 of 9	ENST00000395184.6	NP_001020787.2
ARHGAP24	XM_024454238.2	c.-105-1889A>G		intron_variant	Intron 1 of 8		XP_024310006.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP24	ENST00000395184.6	c.181-1889A>G		intron_variant	Intron 2 of 9	2	NM_001025616.3	ENSP00000378611.1

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76776 AN: 151644 Hom.: 22962 Cov.: 29

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.853

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.629

Gnomad EAS AF: 0.0872

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.543

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

GnomAD4 genome AF: 0.506 AC: 76796 AN: 151762 Hom.: 22961 Cov.: 29 AF XY: 0.495 AC XY: 36696 AN XY: 74106

African (AFR) AF: 0.234 AC: 9681 AN: 41396

American (AMR) AF: 0.458 AC: 6976 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.629 AC: 2181 AN: 3468

East Asian (EAS) AF: 0.0872 AC: 449 AN: 5148

South Asian (SAS) AF: 0.421 AC: 2016 AN: 4794

European-Finnish (FIN) AF: 0.606 AC: 6364 AN: 10508

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.693 AC: 47052 AN: 67908

Other (OTH) AF: 0.540 AC: 1137 AN: 2106

Alfa AF: 0.621 Hom.: 97392

Bravo AF: 0.483

Asia WGS AF: 0.269 AC: 937 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.51
DANN	Benign	0.60
PhyloP100		-0.068
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7692808; hg19: chr4-86641149;