rs346473

Variant names:

• chr4-85980468-G-A
• rs346473
• NM_001025616.3:c.928+2777G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-85980468-G-A
• chr4-85980468-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001025616.3(ARHGAP24):​c.928+2777G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.655 in 152,062 control chromosomes in the GnomAD database, including 33,889 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 0.66 (33889 hom., cov: 32)
• Consequence: ARHGAP24 NM_001025616.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.143
• Publications: 6 publications found

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]

ARHGAP24 Gene-Disease associations (from GenCC):

• familial idiopathic steroid-resistant nephrotic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP24	NM_001025616.3	c.928+2777G>A		intron_variant	Intron 8 of 9	ENST00000395184.6	NP_001020787.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP24	ENST00000395184.6	c.928+2777G>A		intron_variant	Intron 8 of 9	2	NM_001025616.3	ENSP00000378611.1
ARHGAP24	ENST00000264343.4	c.649+2777G>A		intron_variant	Intron 5 of 6	1		ENSP00000264343.4
ARHGAP24	ENST00000395183.6	c.643+2777G>A		intron_variant	Intron 6 of 7	1		ENSP00000378610.2
ARHGAP24	ENST00000514229.5	c.673+2777G>A		intron_variant	Intron 6 of 7	1		ENSP00000425589.1

Frequencies

GnomAD3 genomes AF: 0.655 AC: 99518 AN: 151944 Hom.: 33839 Cov.: 32

Gnomad AFR AF: 0.829

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.696

Gnomad ASJ AF: 0.583

Gnomad EAS AF: 0.807

Gnomad SAS AF: 0.717

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.648

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

GnomAD4 genome AF: 0.655 AC: 99629 AN: 152062 Hom.: 33889 Cov.: 32 AF XY: 0.658 AC XY: 48921 AN XY: 74326

African (AFR) AF: 0.829 AC: 34421 AN: 41510

American (AMR) AF: 0.696 AC: 10642 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.583 AC: 2024 AN: 3472

East Asian (EAS) AF: 0.807 AC: 4170 AN: 5170

South Asian (SAS) AF: 0.717 AC: 3458 AN: 4822

European-Finnish (FIN) AF: 0.508 AC: 5347 AN: 10530

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.552 AC: 37535 AN: 67958

Other (OTH) AF: 0.651 AC: 1377 AN: 2114

Alfa AF: 0.590 Hom.: 14793

Bravo AF: 0.677

Asia WGS AF: 0.750 AC: 2604 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.1
DANN	Benign	0.61
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs346473; hg19: chr4-86901621;