chr19-49677009-C-G

Position:

• chr19-49677009-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000527382.5(PRMT1):​c.-49+749C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 380,340 control chromosomes in the GnomAD database, including 19,951 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (11295 hom., cov: 32)
  • Exomes 𝑓: 0.26 (8656 hom.)
• Consequence: PRMT1 ENST00000527382.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.09

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 19-49677009-C-G is Benign according to our data. Variant chr19-49677009-C-G is described in ClinVar as [Benign]. Clinvar id is 1239630.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRMT1	XM_047438742.1	c.-28+570C>G		intron_variant			XP_047294698.1
PRMT1	XM_047438743.1	c.-28+570C>G		intron_variant			XP_047294699.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRMT1	ENST00000532489.5	c.-49+570C>G		intron_variant		5		ENSP00000433556.1
PRMT1	ENST00000527382.5	c.-49+749C>G		intron_variant		3		ENSP00000432538.1
PRMT1	ENST00000529284.5	c.-49+570C>G		intron_variant		5		ENSP00000432349.1
PRMT1	ENST00000528623.5	c.-155+570C>G		intron_variant		3		ENSP00000434911.1

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53642 AN: 151972 Hom.: 11260 Cov.: 32

Gnomad AFR AF: 0.594

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.319

GnomAD4 exome AF: 0.263 AC: 60011 AN: 228252 Hom.: 8656 AF XY: 0.263 AC XY: 30352 AN XY: 115568

Gnomad4 AFR exome AF: 0.594

Gnomad4 AMR exome AF: 0.303

Gnomad4 ASJ exome AF: 0.262

Gnomad4 EAS exome AF: 0.178

Gnomad4 SAS exome AF: 0.311

Gnomad4 FIN exome AF: 0.221

Gnomad4 NFE exome AF: 0.258

Gnomad4 OTH exome AF: 0.294

GnomAD4 genome AF: 0.353 AC: 53727 AN: 152088 Hom.: 11295 Cov.: 32 AF XY: 0.348 AC XY: 25854 AN XY: 74374

Gnomad4 AFR AF: 0.595

Gnomad4 AMR AF: 0.312

Gnomad4 ASJ AF: 0.260

Gnomad4 EAS AF: 0.182

Gnomad4 SAS AF: 0.315

Gnomad4 FIN AF: 0.214

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.320

Alfa AF: 0.188 Hom.: 438

Bravo AF: 0.370

Asia WGS AF: 0.340 AC: 1178 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 02, 2020	This variant is associated with the following publications: (PMID: 32245889) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	7.4
DANN	Benign	0.76

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs975484; hg19: chr19-50180266;