rs3738579

Positions:

• chr1-182586901-A-G

Variant summary

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

The NM_021133.4(RNASEL):​c.-95T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 1,539,808 control chromosomes in the GnomAD database, including 86,593 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 0.28 (6670 hom., cov: 33)
  • Exomes 𝑓: 0.33 (79923 hom.)
• Consequence: RNASEL NM_021133.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.569

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNASEL	NM_021133.4	c.-95T>C		5_prime_UTR_variant	2/7	ENST00000367559.7
RNASEL	XM_047427096.1	c.-95T>C		5_prime_UTR_variant	2/7
RNASEL	XM_047427106.1	c.-95T>C		5_prime_UTR_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNASEL	ENST00000367559.7	c.-95T>C		5_prime_UTR_variant	2/7	1	NM_021133.4	P1
RNASEL	ENST00000539397.1	c.-95T>C		5_prime_UTR_variant	2/6	2

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41949 AN: 152088 Hom.: 6673 Cov.: 33

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.361

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.291

GnomAD4 exome AF: 0.333 AC: 462718 AN: 1387602 Hom.: 79923 Cov.: 22 AF XY: 0.333 AC XY: 231443 AN XY: 694340

Gnomad4 AFR exome AF: 0.111

Gnomad4 AMR exome AF: 0.173

Gnomad4 ASJ exome AF: 0.300

Gnomad4 EAS exome AF: 0.221

Gnomad4 SAS exome AF: 0.293

Gnomad4 FIN exome AF: 0.373

Gnomad4 NFE exome AF: 0.355

Gnomad4 OTH exome AF: 0.314

GnomAD4 genome AF: 0.276 AC: 41950 AN: 152206 Hom.: 6670 Cov.: 33 AF XY: 0.276 AC XY: 20513 AN XY: 74410

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.286

Gnomad4 EAS AF: 0.240

Gnomad4 SAS AF: 0.291

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.361

Gnomad4 OTH AF: 0.293

Alfa AF: 0.344 Hom.: 15348

Bravo AF: 0.256

Asia WGS AF: 0.288 AC: 1004 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.7
DANN	Benign	0.77

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: rs3738579; hg19: chr1-182556036;