rs346473

chr4-85980468-G-Achr4-85980468-G-C

Variant summary

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

The NM_001025616.3(ARHGAP24):c.928+2777G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.655 in 152,062 control chromosomes in the GnomAD database, including 33,889 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 0.66 (33889 hom., cov: 32)
• Consequence: ARHGAP24 NM_001025616.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.143

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP24	NM_001025616.3	c.928+2777G>A		intron_variant		ENST00000395184.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP24	ENST00000395184.6	c.928+2777G>A		intron_variant		2	NM_001025616.3	P1
ARHGAP24	ENST00000264343.4	c.649+2777G>A		intron_variant		1
ARHGAP24	ENST00000395183.6	c.643+2777G>A		intron_variant		1
ARHGAP24	ENST00000514229.5	c.673+2777G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.655 AC: 99518 AN: 151944 Hom.: 33839 Cov.: 32

Gnomad AFR AF: 0.829

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.696

Gnomad ASJ AF: 0.583

Gnomad EAS AF: 0.807

Gnomad SAS AF: 0.717

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.648

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

GnomAD4 genome AF: 0.655 AC: 99629 AN: 152062 Hom.: 33889 Cov.: 32 AF XY: 0.658 AC XY: 48921 AN XY: 74326

Gnomad4 AFR AF: 0.829

Gnomad4 AMR AF: 0.696

Gnomad4 ASJ AF: 0.583

Gnomad4 EAS AF: 0.807

Gnomad4 SAS AF: 0.717

Gnomad4 FIN AF: 0.508

Gnomad4 NFE AF: 0.552

Gnomad4 OTH AF: 0.651

Alfa AF: 0.589 Hom.: 13230

Bravo AF: 0.677

Asia WGS AF: 0.750 AC: 2604 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	2.1
Dann	Benign	0.61

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: rs346473; hg19: chr4-86901621;