1-182576086-C-T

Variant names:

• chr1-182576086-C-T
• rs672527
• NM_021133.4:c.2039+170G>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.2039+170G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 152,200 control chromosomes in the GnomAD database, including 4,124 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 0.21 (4124 hom., cov: 32)
• Consequence: RNASEL NM_021133.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.668
• Publications: 12 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNASEL	NM_021133.4	c.2039+170G>A		intron_variant	Intron 6 of 6	ENST00000367559.7	NP_066956.1
RNASEL	XM_047427096.1	c.*285G>A		downstream_gene_variant			XP_047283052.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNASEL	ENST00000367559.7	c.2039+170G>A		intron_variant	Intron 6 of 6	1	NM_021133.4	ENSP00000356530.3

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31777 AN: 152082 Hom.: 4123 Cov.: 32

Gnomad AFR AF: 0.0735

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.0867

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.209 AC: 31780 AN: 152200 Hom.: 4124 Cov.: 32 AF XY: 0.208 AC XY: 15448 AN XY: 74410

African (AFR) AF: 0.0734 AC: 3048 AN: 41542

American (AMR) AF: 0.184 AC: 2808 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 817 AN: 3468

East Asian (EAS) AF: 0.0869 AC: 451 AN: 5190

South Asian (SAS) AF: 0.186 AC: 896 AN: 4828

European-Finnish (FIN) AF: 0.323 AC: 3420 AN: 10572

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.288 AC: 19585 AN: 67988

Other (OTH) AF: 0.225 AC: 476 AN: 2112

Alfa AF: 0.260 Hom.: 7015

Bravo AF: 0.193

Asia WGS AF: 0.125 AC: 437 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.79
DANN	Benign	0.29
PhyloP100		-0.67
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: rs672527; hg19: chr1-182545221;