chr4-85600832-G-A

Variant names:

• chr4-85600832-G-A
• rs12506596
• NM_001025616.3:c.180+30111G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001025616.3(ARHGAP24):​c.180+30111G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 152,130 control chromosomes in the GnomAD database, including 7,473 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 0.27 (7473 hom., cov: 33)
• Consequence: ARHGAP24 NM_001025616.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.231
• Publications: 6 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.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.82 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP24	NM_001025616.3	c.180+30111G>A		intron_variant	Intron 2 of 9	ENST00000395184.6	NP_001020787.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP24	ENST00000395184.6	c.180+30111G>A		intron_variant	Intron 2 of 9	2	NM_001025616.3	ENSP00000378611.1
ARHGAP24	ENST00000503995.5	c.180+30111G>A		intron_variant	Intron 2 of 5	1		ENSP00000423206.1
ARHGAP24	ENST00000506421.5	n.317+30111G>A		intron_variant	Intron 2 of 3	3
ARHGAP24	ENST00000509709.1	n.129+30111G>A		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40290 AN: 152012 Hom.: 7460 Cov.: 33

Gnomad AFR AF: 0.0693

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.840

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.288

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

GnomAD4 genome AF: 0.265 AC: 40325 AN: 152130 Hom.: 7473 Cov.: 33 AF XY: 0.276 AC XY: 20520 AN XY: 74362

African (AFR) AF: 0.0694 AC: 2883 AN: 41540

American (AMR) AF: 0.415 AC: 6332 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 988 AN: 3472

East Asian (EAS) AF: 0.840 AC: 4345 AN: 5170

South Asian (SAS) AF: 0.467 AC: 2255 AN: 4828

European-Finnish (FIN) AF: 0.312 AC: 3306 AN: 10584

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.283 AC: 19266 AN: 67962

Other (OTH) AF: 0.294 AC: 621 AN: 2112

Alfa AF: 0.271 Hom.: 1180

Bravo AF: 0.266

Asia WGS AF: 0.579 AC: 2011 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	14
DANN	Benign	0.87
PhyloP100		-0.23
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: rs12506596; hg19: chr4-86521985;