4-85794159-G-T

Variant names:

• chr4-85794159-G-T
• rs7687906
• NM_001025616.3:c.268+72187G>T

Variant summary

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

The NM_001025616.3(ARHGAP24):​c.268+72187G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.841 in 152,164 control chromosomes in the GnomAD database, including 53,868 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 0.84 (53868 hom., cov: 31)
• Consequence: ARHGAP24 NM_001025616.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0280
• Publications: 7 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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP24	NM_001025616.3	c.268+72187G>T		intron_variant	Intron 3 of 9	ENST00000395184.6	NP_001020787.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP24	ENST00000395184.6	c.268+72187G>T		intron_variant	Intron 3 of 9	2	NM_001025616.3	ENSP00000378611.1
ARHGAP24	ENST00000395183.6	c.-18+15194G>T		intron_variant	Intron 1 of 7	1		ENSP00000378610.2
ARHGAP24	ENST00000503995.5	c.268+72187G>T		intron_variant	Intron 3 of 5	1		ENSP00000423206.1
ARHGAP24	ENST00000512201.5	c.-18+72187G>T		intron_variant	Intron 3 of 4	4		ENSP00000426105.1

Frequencies

GnomAD3 genomes AF: 0.841 AC: 127827 AN: 152046 Hom.: 53826 Cov.: 31

Gnomad AFR AF: 0.831

Gnomad AMI AF: 0.942

Gnomad AMR AF: 0.807

Gnomad ASJ AF: 0.914

Gnomad EAS AF: 0.826

Gnomad SAS AF: 0.801

Gnomad FIN AF: 0.822

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.855

Gnomad OTH AF: 0.847

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

GnomAD4 genome AF: 0.841 AC: 127927 AN: 152164 Hom.: 53868 Cov.: 31 AF XY: 0.837 AC XY: 62221 AN XY: 74380

African (AFR) AF: 0.831 AC: 34500 AN: 41496

American (AMR) AF: 0.807 AC: 12336 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.914 AC: 3171 AN: 3470

East Asian (EAS) AF: 0.825 AC: 4263 AN: 5168

South Asian (SAS) AF: 0.801 AC: 3863 AN: 4824

European-Finnish (FIN) AF: 0.822 AC: 8703 AN: 10582

Middle Eastern (MID) AF: 0.878 AC: 258 AN: 294

European-Non Finnish (NFE) AF: 0.855 AC: 58190 AN: 68022

Other (OTH) AF: 0.846 AC: 1784 AN: 2108

Alfa AF: 0.847 Hom.: 68383

Bravo AF: 0.838

Asia WGS AF: 0.828 AC: 2870 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.2
DANN	Benign	0.47
PhyloP100		0.028
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: rs7687906; hg19: chr4-86715312;