rs17010960

Positions:

• chr4-85798761-A-T

Variant summary

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

The NM_001025616.3(ARHGAP24):​c.268+76789A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0796 in 152,276 control chromosomes in the GnomAD database, including 777 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 0.080 (777 hom., cov: 32)
• Consequence: ARHGAP24 NM_001025616.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.429

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP24	NM_001025616.3	c.268+76789A>T		intron_variant		ENST00000395184.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP24	ENST00000395184.6	c.268+76789A>T		intron_variant		2	NM_001025616.3	P1
ARHGAP24	ENST00000395183.6	c.-18+19796A>T		intron_variant		1
ARHGAP24	ENST00000503995.5	c.268+76789A>T		intron_variant		1
ARHGAP24	ENST00000512201.5	c.-18+76789A>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.0796 AC: 12116 AN: 152158 Hom.: 779 Cov.: 32

Gnomad AFR AF: 0.0842

Gnomad AMI AF: 0.0571

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.0634

Gnomad EAS AF: 0.287

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.0103

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0478

Gnomad OTH AF: 0.0707

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

GnomAD4 genome AF: 0.0796 AC: 12120 AN: 152276 Hom.: 777 Cov.: 32 AF XY: 0.0839 AC XY: 6248 AN XY: 74442

Gnomad4 AFR AF: 0.0842

Gnomad4 AMR AF: 0.145

Gnomad4 ASJ AF: 0.0634

Gnomad4 EAS AF: 0.287

Gnomad4 SAS AF: 0.234

Gnomad4 FIN AF: 0.0103

Gnomad4 NFE AF: 0.0478

Gnomad4 OTH AF: 0.0710

Alfa AF: 0.0579 Hom.: 37

Bravo AF: 0.0866

Asia WGS AF: 0.252 AC: 874 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.8
DANN	Benign	0.82

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: rs17010960; hg19: chr4-86719914;