NM_001025616.3:c.268+8339T>C

Variant names:

• chr4-85730311-T-C
• rs7660702
• NM_001025616.3:c.268+8339T>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.268+8339T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 152,040 control chromosomes in the GnomAD database, including 16,088 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 0.43 (16088 hom., cov: 32)
• Consequence: ARHGAP24 NM_001025616.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.825
• Publications: 28 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.89 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP24	NM_001025616.3	c.268+8339T>C		intron_variant	Intron 3 of 9	ENST00000395184.6	NP_001020787.2
ARHGAP24	XM_024454238.2	c.-18+8339T>C		intron_variant	Intron 2 of 8		XP_024310006.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP24	ENST00000395184.6	c.268+8339T>C		intron_variant	Intron 3 of 9	2	NM_001025616.3	ENSP00000378611.1
ARHGAP24	ENST00000503995.5	c.268+8339T>C		intron_variant	Intron 3 of 5	1		ENSP00000423206.1
ARHGAP24	ENST00000512201.5	c.-18+8339T>C		intron_variant	Intron 3 of 4	4		ENSP00000426105.1

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65812 AN: 151922 Hom.: 16068 Cov.: 32

Gnomad AFR AF: 0.555

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.521

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.912

Gnomad SAS AF: 0.581

Gnomad FIN AF: 0.394

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.412

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

GnomAD4 genome AF: 0.433 AC: 65879 AN: 152040 Hom.: 16088 Cov.: 32 AF XY: 0.446 AC XY: 33148 AN XY: 74332

African (AFR) AF: 0.555 AC: 22997 AN: 41470

American (AMR) AF: 0.522 AC: 7966 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.370 AC: 1281 AN: 3466

East Asian (EAS) AF: 0.912 AC: 4720 AN: 5178

South Asian (SAS) AF: 0.580 AC: 2795 AN: 4822

European-Finnish (FIN) AF: 0.394 AC: 4164 AN: 10556

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.306 AC: 20822 AN: 67956

Other (OTH) AF: 0.416 AC: 878 AN: 2112

Alfa AF: 0.355 Hom.: 40934

Bravo AF: 0.448

Asia WGS AF: 0.720 AC: 2502 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.34
DANN	Benign	0.60
PhyloP100		-0.82
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: rs7660702; hg19: chr4-86651464;