chr4-85836983-G-A

Position:

• chr4-85836983-G-A

Variant summary

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

The NM_001025616.3(ARHGAP24):​c.269-86665G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.668 in 152,038 control chromosomes in the GnomAD database, including 34,245 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 0.67 (34245 hom., cov: 32)
• Consequence: ARHGAP24 NM_001025616.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.665

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP24	NM_001025616.3	c.269-86665G>A		intron_variant		ENST00000395184.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP24	ENST00000395184.6	c.269-86665G>A		intron_variant		2	NM_001025616.3	P1

Frequencies

GnomAD3 genomes AF: 0.668 AC: 101493 AN: 151922 Hom.: 34233 Cov.: 32

Gnomad AFR AF: 0.603

Gnomad AMI AF: 0.780

Gnomad AMR AF: 0.654

Gnomad ASJ AF: 0.729

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.660

Gnomad FIN AF: 0.653

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.725

Gnomad OTH AF: 0.667

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

GnomAD4 genome AF: 0.668 AC: 101553 AN: 152038 Hom.: 34245 Cov.: 32 AF XY: 0.661 AC XY: 49136 AN XY: 74312

Gnomad4 AFR AF: 0.604

Gnomad4 AMR AF: 0.654

Gnomad4 ASJ AF: 0.729

Gnomad4 EAS AF: 0.451

Gnomad4 SAS AF: 0.658

Gnomad4 FIN AF: 0.653

Gnomad4 NFE AF: 0.725

Gnomad4 OTH AF: 0.666

Alfa AF: 0.690 Hom.: 4621

Bravo AF: 0.662

Asia WGS AF: 0.566 AC: 1966 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.074
DANN	Benign	0.11

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: rs896656; hg19: chr4-86758136;