rs17010960

Variant names:

• chr4-85798761-A-T
• rs17010960
• NM_001025616.3:c.268+76789A>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.268+76789A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0796 in 152,276 control chromosomes in the GnomAD database, including 777 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 0.080 (777 hom., cov: 32)
• Consequence: ARHGAP24 NM_001025616.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.429
• Publications: 1 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP24	NM_001025616.3	c.268+76789A>T		intron_variant	Intron 3 of 9	ENST00000395184.6	NP_001020787.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP24	ENST00000395184.6	c.268+76789A>T		intron_variant	Intron 3 of 9	2	NM_001025616.3	ENSP00000378611.1
ARHGAP24	ENST00000395183.6	c.-18+19796A>T		intron_variant	Intron 1 of 7	1		ENSP00000378610.2
ARHGAP24	ENST00000503995.5	c.268+76789A>T		intron_variant	Intron 3 of 5	1		ENSP00000423206.1
ARHGAP24	ENST00000512201.5	c.-18+76789A>T		intron_variant	Intron 3 of 4	4		ENSP00000426105.1

Frequencies

GnomAD3 genomes AF: 0.0796 AC: 12116 AN: 152158 Hom.: 779 Cov.: 32

Gnomad AFR AF: 0.0842

Gnomad AMI AF: 0.0571

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.0634

Gnomad EAS AF: 0.287

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.0103

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0478

Gnomad OTH AF: 0.0707

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

GnomAD4 genome AF: 0.0796 AC: 12120 AN: 152276 Hom.: 777 Cov.: 32 AF XY: 0.0839 AC XY: 6248 AN XY: 74442

African (AFR) AF: 0.0842 AC: 3501 AN: 41562

American (AMR) AF: 0.145 AC: 2210 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0634 AC: 220 AN: 3470

East Asian (EAS) AF: 0.287 AC: 1486 AN: 5174

South Asian (SAS) AF: 0.234 AC: 1127 AN: 4824

European-Finnish (FIN) AF: 0.0103 AC: 109 AN: 10622

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0478 AC: 3252 AN: 68012

Other (OTH) AF: 0.0710 AC: 150 AN: 2114

Alfa AF: 0.0579 Hom.: 37

Bravo AF: 0.0866

Asia WGS AF: 0.252 AC: 874 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.8
DANN	Benign	0.82
PhyloP100		0.43
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: rs17010960; hg19: chr4-86719914;