rs516134

Positions:

• chr1-182584558-C-A
• chr1-182584558-C-G
• chr1-182584558-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021133.4(RNASEL):​c.1481-392G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
• Consequence: RNASEL NM_021133.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.448

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNASEL	NM_021133.4	c.1481-392G>T		intron_variant		ENST00000367559.7	NP_066956.1
RNASEL	XM_047427096.1	c.1481-392G>T		intron_variant			XP_047283052.1
RNASEL	XM_047427106.1	c.1481-392G>T		intron_variant			XP_047283062.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNASEL	ENST00000367559.7	c.1481-392G>T		intron_variant		1	NM_021133.4	ENSP00000356530	P1
RNASEL	ENST00000539397.1	c.1481-392G>T		intron_variant		2		ENSP00000440844

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.1
DANN	Benign	0.60

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: rs516134; hg19: chr1-182553693;