rs7692808

Positions:

• chr4-85719996-A-G
• chr4-85719996-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.181-1889A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 151,762 control chromosomes in the GnomAD database, including 22,961 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 0.51 (22961 hom., cov: 29)
• Consequence: ARHGAP24 NM_001025616.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0680

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP24	NM_001025616.3	c.181-1889A>G		intron_variant		ENST00000395184.6	NP_001020787.2
ARHGAP24	XM_024454238.2	c.-105-1889A>G		intron_variant			XP_024310006.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP24	ENST00000395184.6	c.181-1889A>G		intron_variant		2	NM_001025616.3	ENSP00000378611	P1

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76776 AN: 151644 Hom.: 22962 Cov.: 29

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.853

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.629

Gnomad EAS AF: 0.0872

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.543

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

GnomAD4 genome AF: 0.506 AC: 76796 AN: 151762 Hom.: 22961 Cov.: 29 AF XY: 0.495 AC XY: 36696 AN XY: 74106

Gnomad4 AFR AF: 0.234

Gnomad4 AMR AF: 0.458

Gnomad4 ASJ AF: 0.629

Gnomad4 EAS AF: 0.0872

Gnomad4 SAS AF: 0.421

Gnomad4 FIN AF: 0.606

Gnomad4 NFE AF: 0.693

Gnomad4 OTH AF: 0.540

Alfa AF: 0.638 Hom.: 38591

Bravo AF: 0.483

Asia WGS AF: 0.269 AC: 937 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.51
DANN	Benign	0.60

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: rs7692808; hg19: chr4-86641149;