rs4693716

Positions:

• chr4-85611758-C-A
• chr4-85611758-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001025616.3(ARHGAP24):​c.180+41037C>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 152,080 control chromosomes in the GnomAD database, including 7,466 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 (7466 hom., cov: 32)
• Consequence: ARHGAP24 NM_001025616.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.475

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• 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/exons	MANE	Protein	UniProt
ARHGAP24	NM_001025616.3	c.180+41037C>A		intron_variant		ENST00000395184.6	NP_001020787.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP24	ENST00000395184.6	c.180+41037C>A		intron_variant		2	NM_001025616.3	ENSP00000378611	P1

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40282 AN: 151962 Hom.: 7453 Cov.: 32

Gnomad AFR AF: 0.0694

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.841

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.290

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

GnomAD4 genome AF: 0.265 AC: 40317 AN: 152080 Hom.: 7466 Cov.: 32 AF XY: 0.276 AC XY: 20515 AN XY: 74336

Gnomad4 AFR AF: 0.0695

Gnomad4 AMR AF: 0.415

Gnomad4 ASJ AF: 0.285

Gnomad4 EAS AF: 0.841

Gnomad4 SAS AF: 0.467

Gnomad4 FIN AF: 0.312

Gnomad4 NFE AF: 0.283

Gnomad4 OTH AF: 0.296

Alfa AF: 0.270 Hom.: 3309

Bravo AF: 0.266

Asia WGS AF: 0.580 AC: 2015 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs4693716; hg19: chr4-86532911;