rs10516750

Variant names:

• chr4-85563778-A-T
• rs10516750
• NM_001025616.3:c.-20-6744A>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.-20-6744A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0997 in 152,256 control chromosomes in the GnomAD database, including 1,083 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 0.10 (1083 hom., cov: 32)
• Consequence: ARHGAP24 NM_001025616.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.292
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP24	NM_001025616.3	c.-20-6744A>T		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.-20-6744A>T		intron_variant	Intron 1 of 9	2	NM_001025616.3	ENSP00000378611.1
ARHGAP24	ENST00000503995.5	c.-20-6744A>T		intron_variant	Intron 1 of 5	1		ENSP00000423206.1
ARHGAP24	ENST00000505856.1	n.75-6744A>T		intron_variant	Intron 1 of 1	2
ARHGAP24	ENST00000506421.5	n.118-6744A>T		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes AF: 0.0997 AC: 15162 AN: 152138 Hom.: 1078 Cov.: 32

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0664

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.0114

Gnomad SAS AF: 0.0265

Gnomad FIN AF: 0.0552

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0626

Gnomad OTH AF: 0.101

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

GnomAD4 genome AF: 0.0997 AC: 15181 AN: 152256 Hom.: 1083 Cov.: 32 AF XY: 0.0976 AC XY: 7270 AN XY: 74450

African (AFR) AF: 0.203 AC: 8430 AN: 41528

American (AMR) AF: 0.0662 AC: 1013 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 445 AN: 3470

East Asian (EAS) AF: 0.0114 AC: 59 AN: 5182

South Asian (SAS) AF: 0.0265 AC: 128 AN: 4828

European-Finnish (FIN) AF: 0.0552 AC: 586 AN: 10616

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.0626 AC: 4259 AN: 68022

Other (OTH) AF: 0.0994 AC: 210 AN: 2112

Alfa AF: 0.0846 Hom.: 94

Bravo AF: 0.104

Asia WGS AF: 0.0330 AC: 115 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	4.7
DANN	Benign	0.73
PhyloP100		-0.29
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: rs10516750; hg19: chr4-86484931;