4-85644320-T-C

Variant names:

• chr4-85644320-T-C
• rs1384134
• NM_001025616.3:c.180+73599T>C

Variant summary

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

The NM_001025616.3(ARHGAP24):​c.180+73599T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 152,046 control chromosomes in the GnomAD database, including 7,434 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 0.26 (7434 hom., cov: 32)
• Consequence: ARHGAP24 NM_001025616.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.610
• 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

LOC105377319 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.819 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP24	NM_001025616.3	c.180+73599T>C		intron_variant	Intron 2 of 9	ENST00000395184.6	NP_001020787.2
LOC105377319	XR_007058168.1	n.816T>C		non_coding_transcript_exon_variant	Exon 1 of 4
LOC105377319	XR_938955.4	n.816T>C		non_coding_transcript_exon_variant	Exon 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP24	ENST00000395184.6	c.180+73599T>C		intron_variant	Intron 2 of 9	2	NM_001025616.3	ENSP00000378611.1

Frequencies

GnomAD3 genomes AF: 0.263 AC: 40002 AN: 151928 Hom.: 7422 Cov.: 32

Gnomad AFR AF: 0.0643

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.840

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.287

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

GnomAD4 genome AF: 0.263 AC: 40029 AN: 152046 Hom.: 7434 Cov.: 32 AF XY: 0.274 AC XY: 20375 AN XY: 74316

African (AFR) AF: 0.0642 AC: 2668 AN: 41548

American (AMR) AF: 0.413 AC: 6308 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 990 AN: 3468

East Asian (EAS) AF: 0.840 AC: 4334 AN: 5158

South Asian (SAS) AF: 0.467 AC: 2255 AN: 4826

European-Finnish (FIN) AF: 0.312 AC: 3291 AN: 10556

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.283 AC: 19231 AN: 67912

Other (OTH) AF: 0.293 AC: 620 AN: 2114

Alfa AF: 0.274 Hom.: 1208

Bravo AF: 0.264

Asia WGS AF: 0.579 AC: 2012 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.2
DANN	Benign	0.62
PhyloP100		0.61
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: rs1384134; hg19: chr4-86565473;