rs1966862

chr4-85766908-A-G

Variant summary

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

The NM_001025616.3(ARHGAP24):c.268+44936A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,188 control chromosomes in the GnomAD database, including 2,743 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 0.15 (2743 hom., cov: 32)
• Consequence: ARHGAP24 NM_001025616.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.748

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 (EAS) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP24	NM_001025616.3	c.268+44936A>G		intron_variant		ENST00000395184.6
ARHGAP24	XM_024454238.2	c.-18+44936A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP24	ENST00000395184.6	c.268+44936A>G		intron_variant		2	NM_001025616.3	P1
ARHGAP24	ENST00000503995.5	c.268+44936A>G		intron_variant		1
ARHGAP24	ENST00000512201.5	c.-18+44936A>G		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23335 AN: 152070 Hom.: 2743 Cov.: 32

Gnomad AFR AF: 0.0947

Gnomad AMI AF: 0.0855

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.661

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.154

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

GnomAD4 genome AF: 0.153 AC: 23355 AN: 152188 Hom.: 2743 Cov.: 32 AF XY: 0.160 AC XY: 11924 AN XY: 74412

Gnomad4 AFR AF: 0.0946

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.159

Gnomad4 EAS AF: 0.660

Gnomad4 SAS AF: 0.317

Gnomad4 FIN AF: 0.126

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.159

Alfa AF: 0.146 Hom.: 881

Bravo AF: 0.158

Asia WGS AF: 0.462 AC: 1600 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	0.58
Dann	Benign	0.54

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: rs1966862; hg19: chr4-86688061;