ENST00000463483.5:n.129+4405C>T

Variant names:

• chr2-68684134-C-T
• rs13423988
• ENST00000463483.5:n.129+4405C>T

Variant summary

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

The ENST00000463483.5(ARHGAP25):​n.129+4405C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 152,002 control chromosomes in the GnomAD database, including 5,794 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 0.26 (5794 hom., cov: 32)
• Consequence: ARHGAP25 ENST00000463483.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.397
• Publications: 6 publications found

Genes affected

ARHGAP25 (HGNC:28951): (Rho GTPase activating protein 25) ARHGAPs, such as ARHGAP25, encode negative regulators of Rho GTPases (see ARHA; MIM 165390), which are implicated in actin remodeling, cell polarity, and cell migration (Katoh and Katoh, 2004 [PubMed 15254788]).[supplied by OMIM, Mar 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP25	ENST00000463483.5	n.129+4405C>T		intron_variant	Intron 1 of 7	2
ARHGAP25	ENST00000481684.5	n.250+4039C>T		intron_variant	Intron 1 of 5	3
ARHGAP25	ENST00000491237.5	n.134+4039C>T		intron_variant	Intron 1 of 3	4

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39515 AN: 151884 Hom.: 5781 Cov.: 32

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.239

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

GnomAD4 genome AF: 0.260 AC: 39554 AN: 152002 Hom.: 5794 Cov.: 32 AF XY: 0.265 AC XY: 19676 AN XY: 74300

African (AFR) AF: 0.394 AC: 16322 AN: 41410

American (AMR) AF: 0.267 AC: 4080 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 565 AN: 3468

East Asian (EAS) AF: 0.331 AC: 1708 AN: 5166

South Asian (SAS) AF: 0.298 AC: 1439 AN: 4824

European-Finnish (FIN) AF: 0.256 AC: 2703 AN: 10558

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.177 AC: 12056 AN: 67982

Other (OTH) AF: 0.239 AC: 505 AN: 2110

Alfa AF: 0.201 Hom.: 9369

Bravo AF: 0.265

Asia WGS AF: 0.314 AC: 1091 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	1.6
DANN	Benign	0.58
PhyloP100		-0.40

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs13423988; hg19: chr2-68911266;