chr4-85766908-A-G

Variant names:

• chr4-85766908-A-G
• rs1966862
• NM_001025616.3:c.268+44936A>G

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+44936A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,188 control chromosomes in the GnomAD database, including 2,743 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 0.15 (2743 hom., cov: 32)
• Consequence: ARHGAP24 NM_001025616.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.748
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP24	NM_001025616.3	c.268+44936A>G		intron_variant	Intron 3 of 9	ENST00000395184.6	NP_001020787.2
ARHGAP24	XM_024454238.2	c.-18+44936A>G		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+44936A>G		intron_variant	Intron 3 of 9	2	NM_001025616.3	ENSP00000378611.1
ARHGAP24	ENST00000503995.5	c.268+44936A>G		intron_variant	Intron 3 of 5	1		ENSP00000423206.1
ARHGAP24	ENST00000512201.5	c.-18+44936A>G		intron_variant	Intron 3 of 4	4		ENSP00000426105.1

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23335 AN: 152070 Hom.: 2743 Cov.: 32

Gnomad AFR AF: 0.0947

Gnomad AMI AF: 0.0855

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.661

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.154

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

GnomAD4 genome AF: 0.153 AC: 23355 AN: 152188 Hom.: 2743 Cov.: 32 AF XY: 0.160 AC XY: 11924 AN XY: 74412

African (AFR) AF: 0.0946 AC: 3933 AN: 41568

American (AMR) AF: 0.206 AC: 3144 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 551 AN: 3468

East Asian (EAS) AF: 0.660 AC: 3424 AN: 5184

South Asian (SAS) AF: 0.317 AC: 1527 AN: 4816

European-Finnish (FIN) AF: 0.126 AC: 1333 AN: 10592

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.132 AC: 8978 AN: 67942

Other (OTH) AF: 0.159 AC: 336 AN: 2114

Alfa AF: 0.144 Hom.: 1163

Bravo AF: 0.158

Asia WGS AF: 0.462 AC: 1600 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.58
DANN	Benign	0.54
PhyloP100		-0.75
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: rs1966862; hg19: chr4-86688061;