rs1481779

Positions:

• chr4-85515902-G-A
• chr4-85515902-G-C
• chr4-85515902-G-T

Variant summary

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

The NM_001025616.3(ARHGAP24):​c.-21+40343G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 152,026 control chromosomes in the GnomAD database, including 25,398 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 0.55 (25398 hom., cov: 31)
• Consequence: ARHGAP24 NM_001025616.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.775 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP24	NM_001025616.3	c.-21+40343G>A		intron_variant		ENST00000395184.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP24	ENST00000395184.6	c.-21+40343G>A		intron_variant		2	NM_001025616.3	P1
ARHGAP24	ENST00000503995.5	c.-21+40343G>A		intron_variant		1
ARHGAP24	ENST00000505856.1	n.74+40343G>A		intron_variant, non_coding_transcript_variant		2
ARHGAP24	ENST00000506421.5	n.117+40343G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82911 AN: 151908 Hom.: 25391 Cov.: 31

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.758

Gnomad AMR AF: 0.551

Gnomad ASJ AF: 0.580

Gnomad EAS AF: 0.795

Gnomad SAS AF: 0.692

Gnomad FIN AF: 0.728

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.663

Gnomad OTH AF: 0.550

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

GnomAD4 genome AF: 0.546 AC: 82946 AN: 152026 Hom.: 25398 Cov.: 31 AF XY: 0.552 AC XY: 41017 AN XY: 74300

Gnomad4 AFR AF: 0.249

Gnomad4 AMR AF: 0.551

Gnomad4 ASJ AF: 0.580

Gnomad4 EAS AF: 0.795

Gnomad4 SAS AF: 0.694

Gnomad4 FIN AF: 0.728

Gnomad4 NFE AF: 0.663

Gnomad4 OTH AF: 0.551

Alfa AF: 0.615 Hom.: 15956

Bravo AF: 0.515

Asia WGS AF: 0.714 AC: 2483 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.50
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: rs1481779; hg19: chr4-86437055;