rs3749132

Variant names:

• chr2-68826365-G-A
• rs3749132
• NM_001007231.3:c.*171G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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]

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

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ARHGAP25	NM_001007231.3	c.*171G>A		3_prime_UTR_variant	Exon 11 of 11	ENST00000409202.8	NP_001007232.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP25	ENST00000409202.8	c.*171G>A		3_prime_UTR_variant	Exon 11 of 11	2	NM_001007231.3	ENSP00000386911.3

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

African (AFR) AF: 0.0122 AC: 196 AN: 16120

American (AMR) AF: 0.0505 AC: 1747 AN: 34604

Ashkenazi Jewish (ASJ) AF: 0.0508 AC: 1016 AN: 19990

East Asian (EAS) AF: 0.0540 AC: 1730 AN: 32014

South Asian (SAS) AF: 0.0467 AC: 2906 AN: 62218

European-Finnish (FIN) AF: 0.0496 AC: 1744 AN: 35194

Middle Eastern (MID) AF: 0.0464 AC: 116 AN: 2498

European-Non Finnish (NFE) AF: 0.0578 AC: 19483 AN: 337278

Other (OTH) AF: 0.0517 AC: 1608 AN: 31088

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

African (AFR) AF: 0.0131 AC: 546 AN: 41546

American (AMR) AF: 0.0416 AC: 637 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0504 AC: 175 AN: 3470

East Asian (EAS) AF: 0.0649 AC: 336 AN: 5174

South Asian (SAS) AF: 0.0475 AC: 229 AN: 4820

European-Finnish (FIN) AF: 0.0534 AC: 565 AN: 10588

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0568 AC: 3861 AN: 68010

Other (OTH) AF: 0.0456 AC: 96 AN: 2106

Alfa AF: 0.0531 Hom.: 300

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
PhyloP100		0.30
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: rs3749132; hg19: chr2-69053497;