Genetic Variant ARHGAP24:c.180+40558G>T (chr4-85611279-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001025616.3(ARHGAP24):c.180+40558G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 151,940 control chromosomes in the GnomAD database, including 9,352 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 0.33 ( 9352 hom., cov: 32)

Consequence

ARHGAP24
NM_001025616.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.273

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 link	c.180+40558G>T		intron_variant	Intron 2 of 9	ENST00000395184.6	NP_001020787.2	Q8N264-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP24	ENST00000395184.6 link	c.180+40558G>T		intron_variant	Intron 2 of 9	2	NM_001025616.3	ENSP00000378611.1		Q8N264-1

Frequencies

GnomAD3 genomes

AF:

0.331

AC:

50188

AN:

151822

Hom.:

9333

Cov.:

show subpopulations

Gnomad AFR

AF:

0.295

Gnomad AMI

AF:

0.275

Gnomad AMR

AF:

0.440

Gnomad ASJ

AF:

0.285

Gnomad EAS

AF:

0.841

Gnomad SAS

AF:

0.468

Gnomad FIN

AF:

0.312

Gnomad MID

AF:

0.294

Gnomad NFE

AF:

0.285

Gnomad OTH

AF:

0.342

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

GnomAD4 genome

AF:

0.331

AC:

50257

AN:

151940

Hom.:

9352

Cov.:

AF XY:

0.340

AC XY:

25286

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.295

Gnomad4 AMR

AF:

0.441

Gnomad4 ASJ

AF:

0.285

Gnomad4 EAS

AF:

0.841

Gnomad4 SAS

AF:

0.468

Gnomad4 FIN

AF:

0.312

Gnomad4 NFE

AF:

0.285

Gnomad4 OTH

AF:

0.347

Alfa

AF:

0.310

Hom.:

1378

Bravo

AF:

0.340

Asia WGS

AF:

0.589

AC:

2043

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.48

DANN

Benign

0.25

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over