4-85654584-T-G

Variant names:

• chr4-85654584-T-G
• rs12644260
• NM_001025616.3:c.181-67301T>G

Variant summary

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

The NM_001025616.3(ARHGAP24):​c.181-67301T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 151,930 control chromosomes in the GnomAD database, including 11,120 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 0.36 (11120 hom., cov: 31)
• Consequence: ARHGAP24 NM_001025616.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.174
• Publications: 4 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

LOC105377319 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• 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.181-67301T>G		intron_variant	Intron 2 of 9	ENST00000395184.6	NP_001020787.2
LOC105377319	XR_007058168.1	n.4065+1462T>G		intron_variant	Intron 2 of 3
LOC105377319	XR_938955.4	n.4065+1462T>G		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP24	ENST00000395184.6	c.181-67301T>G		intron_variant	Intron 2 of 9	2	NM_001025616.3	ENSP00000378611.1

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55111 AN: 151814 Hom.: 11096 Cov.: 31

Gnomad AFR AF: 0.410

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.841

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.365

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

GnomAD4 genome AF: 0.363 AC: 55196 AN: 151930 Hom.: 11120 Cov.: 31 AF XY: 0.372 AC XY: 27628 AN XY: 74252

African (AFR) AF: 0.411 AC: 17020 AN: 41442

American (AMR) AF: 0.451 AC: 6865 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 991 AN: 3468

East Asian (EAS) AF: 0.841 AC: 4341 AN: 5164

South Asian (SAS) AF: 0.467 AC: 2253 AN: 4820

European-Finnish (FIN) AF: 0.312 AC: 3287 AN: 10548

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.284 AC: 19314 AN: 67936

Other (OTH) AF: 0.370 AC: 782 AN: 2112

Alfa AF: 0.320 Hom.: 2107

Bravo AF: 0.377

Asia WGS AF: 0.599 AC: 2081 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.8
DANN	Benign	0.41
PhyloP100		-0.17
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: rs12644260; hg19: chr4-86575737;