rs10415880

Positions:

• chr19-49685899-G-A

Variant summary

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

The NM_001536.6(PRMT1):​c.760-194G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 1,408,698 control chromosomes in the GnomAD database, including 70,104 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 0.29 (6812 hom., cov: 31)
  • Exomes 𝑓: 0.31 (63292 hom.)
• Consequence: PRMT1 NM_001536.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.975

Genes affected

PRMT1 (HGNC:5187): (protein arginine methyltransferase 1) This gene encodes a member of the protein arginine N-methyltransferase (PRMT) family. Post-translational modification of target proteins by PRMTs plays an important regulatory role in many biological processes, whereby PRMTs methylate arginine residues by transferring methyl groups from S-adenosyl-L-methionine to terminal guanidino nitrogen atoms. The encoded protein is a type I PRMT and is responsible for the majority of cellular arginine methylation activity. Increased expression of this gene may play a role in many types of cancer. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 5. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRMT1	NM_001536.6	c.760-194G>A		intron_variant		ENST00000454376.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRMT1	ENST00000454376.7	c.760-194G>A		intron_variant		1	NM_001536.6	P4

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44554 AN: 151786 Hom.: 6803 Cov.: 31

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.0216

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.284

GnomAD4 exome AF: 0.309 AC: 388800 AN: 1256794 Hom.: 63292 Cov.: 34 AF XY: 0.306 AC XY: 185844 AN XY: 607908

Gnomad4 AFR exome AF: 0.327

Gnomad4 AMR exome AF: 0.188

Gnomad4 ASJ exome AF: 0.273

Gnomad4 EAS exome AF: 0.0175

Gnomad4 SAS exome AF: 0.168

Gnomad4 FIN exome AF: 0.296

Gnomad4 NFE exome AF: 0.330

Gnomad4 OTH exome AF: 0.307

GnomAD4 genome AF: 0.294 AC: 44588 AN: 151904 Hom.: 6812 Cov.: 31 AF XY: 0.286 AC XY: 21219 AN XY: 74234

Gnomad4 AFR AF: 0.318

Gnomad4 AMR AF: 0.219

Gnomad4 ASJ AF: 0.273

Gnomad4 EAS AF: 0.0217

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.319

Gnomad4 NFE AF: 0.322

Gnomad4 OTH AF: 0.284

Alfa AF: 0.313 Hom.: 9591

Bravo AF: 0.289

Asia WGS AF: 0.122 AC: 424 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.75
DANN	Benign	0.63

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: rs10415880; hg19: chr19-50189156;