rs672527

chr1-182576086-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.86).
• 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/exons	MANE	UniProt
RNASEL	NM_021133.4	c.2039+170G>A		intron_variant		ENST00000367559.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNASEL	ENST00000367559.7	c.2039+170G>A		intron_variant		1	NM_021133.4	P1

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

Gnomad4 AFR AF: 0.0734

Gnomad4 AMR AF: 0.184

Gnomad4 ASJ AF: 0.236

Gnomad4 EAS AF: 0.0869

Gnomad4 SAS AF: 0.186

Gnomad4 FIN AF: 0.323

Gnomad4 NFE AF: 0.288

Gnomad4 OTH AF: 0.225

Alfa AF: 0.270 Hom.: 5686

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

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: rs672527; hg19: chr1-182545221;