4-85762407-G-C

Position:

• chr4-85762407-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.268+40435G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 152,008 control chromosomes in the GnomAD database, including 18,197 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 0.45 (18197 hom., cov: 32)
• Consequence: ARHGAP24 NM_001025616.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0350

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.61 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP24	NM_001025616.3	c.268+40435G>C		intron_variant		ENST00000395184.6
ARHGAP24	XM_024454238.2	c.-18+40435G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP24	ENST00000395184.6	c.268+40435G>C		intron_variant		2	NM_001025616.3	P1
ARHGAP24	ENST00000503995.5	c.268+40435G>C		intron_variant		1
ARHGAP24	ENST00000512201.5	c.-18+40435G>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68553 AN: 151890 Hom.: 18198 Cov.: 32

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.768

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.0598

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.548

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.615

Gnomad OTH AF: 0.478

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

GnomAD4 genome AF: 0.451 AC: 68562 AN: 152008 Hom.: 18197 Cov.: 32 AF XY: 0.441 AC XY: 32756 AN XY: 74296

Gnomad4 AFR AF: 0.215

Gnomad4 AMR AF: 0.410

Gnomad4 ASJ AF: 0.565

Gnomad4 EAS AF: 0.0599

Gnomad4 SAS AF: 0.356

Gnomad4 FIN AF: 0.548

Gnomad4 NFE AF: 0.615

Gnomad4 OTH AF: 0.475

Alfa AF: 0.370 Hom.: 1088

Bravo AF: 0.431

Asia WGS AF: 0.211 AC: 736 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.9
DANN	Benign	0.44

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: rs11732231; hg19: chr4-86683560;