rs12135247

Positions:

• chr1-182574802-T-C

Variant summary

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

The NM_021133.4(RNASEL):​c.*590A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 231,212 control chromosomes in the GnomAD database, including 9,013 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 (5627 hom., cov: 29)
  • Exomes 𝑓: 0.28 (3386 hom.)
• Consequence: RNASEL NM_021133.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44

Genes affected

RNASEL (HGNC:10050): (ribonuclease L) This gene encodes a component of the interferon-regulated 2-5A system that functions in the antiviral and antiproliferative roles of interferons. The protein is involved in innate immunity and is active against multiple RNA viruses, including the influenza and SARS-CoV-2 viruses. Mutations in this gene have been associated with predisposition to prostate cancer and this gene is a candidate for the hereditary prostate cancer 1 (HPC1) allele. [provided by RefSeq, Nov 2021]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNASEL	NM_021133.4	c.*590A>G		3_prime_UTR_variant	7/7	ENST00000367559.7	NP_066956.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNASEL	ENST00000367559.7	c.*590A>G		3_prime_UTR_variant	7/7	1	NM_021133.4	ENSP00000356530	P1

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39432 AN: 150044 Hom.: 5625 Cov.: 29

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.277

GnomAD4 exome AF: 0.280 AC: 22670 AN: 81050 Hom.: 3386 Cov.: 0 AF XY: 0.284 AC XY: 10598 AN XY: 37316

Gnomad4 AFR exome AF: 0.203

Gnomad4 AMR exome AF: 0.284

Gnomad4 ASJ exome AF: 0.403

Gnomad4 EAS exome AF: 0.169

Gnomad4 SAS exome AF: 0.394

Gnomad4 FIN exome AF: 0.210

Gnomad4 NFE exome AF: 0.294

Gnomad4 OTH exome AF: 0.288

GnomAD4 genome AF: 0.263 AC: 39441 AN: 150162 Hom.: 5627 Cov.: 29 AF XY: 0.263 AC XY: 19215 AN XY: 73158

Gnomad4 AFR AF: 0.192

Gnomad4 AMR AF: 0.323

Gnomad4 ASJ AF: 0.425

Gnomad4 EAS AF: 0.186

Gnomad4 SAS AF: 0.376

Gnomad4 FIN AF: 0.192

Gnomad4 NFE AF: 0.289

Gnomad4 OTH AF: 0.279

Alfa AF: 0.275 Hom.: 1773

Bravo AF: 0.267

Asia WGS AF: 0.298 AC: 1037 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.54
DANN	Benign	0.54

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: rs12135247; hg19: chr1-182543937;