chr1-182584558-C-T

Variant names:

• chr1-182584558-C-T
• rs516134
• NM_021133.4:c.1481-392G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021133.4(RNASEL):​c.1481-392G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.935 in 152,264 control chromosomes in the GnomAD database, including 66,916 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 0.93 (66916 hom., cov: 31)
• Consequence: RNASEL NM_021133.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.448
• Publications: 8 publications found

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]

RNASEL Gene-Disease associations (from GenCC):

• prostate cancer, hereditary, 1

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021133.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNASEL	NM_021133.4	MANE Select	c.1481-392G>A		intron	N/A	NP_066956.1	Q05823-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNASEL	ENST00000367559.7	TSL:1 MANE Select	c.1481-392G>A		intron	N/A	ENSP00000356530.3	Q05823-1
	RNASEL	ENST00000946546.1		c.1481-392G>A		intron	N/A	ENSP00000616605.1
	RNASEL	ENST00000890859.1		c.1481-392G>A		intron	N/A	ENSP00000560918.1

Frequencies

GnomAD3 genomes AF: 0.935 AC: 142267 AN: 152146 Hom.: 66873 Cov.: 31

Gnomad AFR AF: 0.827

Gnomad AMI AF: 0.968

Gnomad AMR AF: 0.969

Gnomad ASJ AF: 0.991

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.992

Gnomad FIN AF: 0.988

Gnomad MID AF: 0.991

Gnomad NFE AF: 0.972

Gnomad OTH AF: 0.953

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

GnomAD4 genome AF: 0.935 AC: 142365 AN: 152264 Hom.: 66916 Cov.: 31 AF XY: 0.938 AC XY: 69861 AN XY: 74468

African (AFR) AF: 0.827 AC: 34326 AN: 41502

American (AMR) AF: 0.969 AC: 14825 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.991 AC: 3441 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5176 AN: 5176

South Asian (SAS) AF: 0.993 AC: 4794 AN: 4830

European-Finnish (FIN) AF: 0.988 AC: 10493 AN: 10622

Middle Eastern (MID) AF: 0.990 AC: 291 AN: 294

European-Non Finnish (NFE) AF: 0.972 AC: 66119 AN: 68040

Other (OTH) AF: 0.953 AC: 2017 AN: 2116

Alfa AF: 0.935 Hom.: 11498

Bravo AF: 0.927

Asia WGS AF: 0.987 AC: 3432 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.55
PhyloP100		0.45
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: rs516134; hg19: chr1-182553693;