4-85642011-T-A

Position:

• chr4-85642011-T-A

Variant summary

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

The NM_001025616.3(ARHGAP24):​c.180+71290T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 152,002 control chromosomes in the GnomAD database, including 9,644 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 0.34 (9644 hom., cov: 32)
• Consequence: ARHGAP24 NM_001025616.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.587

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=-0.97).
• 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/exons	MANE	UniProt
ARHGAP24	NM_001025616.3	c.180+71290T>A		intron_variant		ENST00000395184.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP24	ENST00000395184.6	c.180+71290T>A		intron_variant		2	NM_001025616.3	P1

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51143 AN: 151884 Hom.: 9625 Cov.: 32

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.840

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.347

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

GnomAD4 genome AF: 0.337 AC: 51214 AN: 152002 Hom.: 9644 Cov.: 32 AF XY: 0.347 AC XY: 25753 AN XY: 74310

Gnomad4 AFR AF: 0.319

Gnomad4 AMR AF: 0.442

Gnomad4 ASJ AF: 0.285

Gnomad4 EAS AF: 0.840

Gnomad4 SAS AF: 0.467

Gnomad4 FIN AF: 0.311

Gnomad4 NFE AF: 0.284

Gnomad4 OTH AF: 0.353

Alfa AF: 0.294 Hom.: 947

Bravo AF: 0.348

Asia WGS AF: 0.593 AC: 2060 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.3
DANN	Benign	0.37

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: rs10000472; hg19: chr4-86563164; COSMIC: COSV67846655;