rs3749132

chr2-68826365-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001007231.3(ARHGAP25):c.*171G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0512 in 723,226 control chromosomes in the GnomAD database, including 1,078 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 0.043 (171 hom., cov: 31)
  • Exomes 𝑓: 0.053 (907 hom.)
• Consequence: ARHGAP25 NM_001007231.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.304

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]

LINC01890 (HGNC:52709): (long intergenic non-protein coding RNA 1890)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP25	NM_001007231.3	c.*171G>A		3_prime_UTR_variant	11/11	ENST00000409202.8
LINC01890	NR_183884.1	n.1163-3363C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP25	ENST00000409202.8	c.*171G>A		3_prime_UTR_variant	11/11	2	NM_001007231.3	P1
LINC01890	ENST00000655209.1	n.1163-3363C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0428 AC: 6506 AN: 152104 Hom.: 171 Cov.: 31

Gnomad AFR AF: 0.0132

Gnomad AMI AF: 0.0473

Gnomad AMR AF: 0.0419

Gnomad ASJ AF: 0.0504

Gnomad EAS AF: 0.0652

Gnomad SAS AF: 0.0481

Gnomad FIN AF: 0.0534

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0568

Gnomad OTH AF: 0.0451

GnomAD4 exome AF: 0.0535 AC: 30546 AN: 571004 Hom.: 907 Cov.: 6 AF XY: 0.0532 AC XY: 16377 AN XY: 307864

Gnomad4 AFR exome AF: 0.0122

Gnomad4 AMR exome AF: 0.0505

Gnomad4 ASJ exome AF: 0.0508

Gnomad4 EAS exome AF: 0.0540

Gnomad4 SAS exome AF: 0.0467

Gnomad4 FIN exome AF: 0.0496

Gnomad4 NFE exome AF: 0.0578

Gnomad4 OTH exome AF: 0.0517

GnomAD4 genome AF: 0.0427 AC: 6499 AN: 152222 Hom.: 171 Cov.: 31 AF XY: 0.0423 AC XY: 3147 AN XY: 74426

Gnomad4 AFR AF: 0.0131

Gnomad4 AMR AF: 0.0416

Gnomad4 ASJ AF: 0.0504

Gnomad4 EAS AF: 0.0649

Gnomad4 SAS AF: 0.0475

Gnomad4 FIN AF: 0.0534

Gnomad4 NFE AF: 0.0568

Gnomad4 OTH AF: 0.0456

Alfa AF: 0.0530 Hom.: 236

Bravo AF: 0.0412

Asia WGS AF: 0.0570 AC: 197 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	2.8
Dann	Benign	0.75

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

Publications

LitVar

Other links and lift over

dbSNP: rs3749132; hg19: chr2-69053497;