1-182573716-G-C

Variant names:

• chr1-182573716-G-C
• rs1048260
• NM_021133.4:c.*1676C>G

Variant summary

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

The NM_021133.4(RNASEL):​c.*1676C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 182,562 control chromosomes in the GnomAD database, including 6,760 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 0.26 (5633 hom., cov: 33)
  • Exomes 𝑓: 0.26 (1127 hom.)
• Consequence: RNASEL NM_021133.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0980

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 (SAS) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNASEL	NM_021133.4	c.*1676C>G		3_prime_UTR_variant	Exon 7 of 7	ENST00000367559.7	NP_066956.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNASEL	ENST00000367559	c.*1676C>G		3_prime_UTR_variant	Exon 7 of 7	1	NM_021133.4	ENSP00000356530.3

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39778 AN: 152040 Hom.: 5629 Cov.: 33

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.273

GnomAD4 exome AF: 0.265 AC: 8045 AN: 30404 Hom.: 1127 Cov.: 0 AF XY: 0.270 AC XY: 3788 AN XY: 14010

Gnomad4 AFR exome AF: 0.187

Gnomad4 AMR exome AF: 0.315

Gnomad4 ASJ exome AF: 0.354

Gnomad4 EAS exome AF: 0.171

Gnomad4 SAS exome AF: 0.372

Gnomad4 FIN exome AF: 0.357

Gnomad4 NFE exome AF: 0.284

Gnomad4 OTH exome AF: 0.284

GnomAD4 genome AF: 0.262 AC: 39794 AN: 152158 Hom.: 5633 Cov.: 33 AF XY: 0.262 AC XY: 19474 AN XY: 74400

Gnomad4 AFR AF: 0.191

Gnomad4 AMR AF: 0.345

Gnomad4 ASJ AF: 0.374

Gnomad4 EAS AF: 0.185

Gnomad4 SAS AF: 0.382

Gnomad4 FIN AF: 0.192

Gnomad4 NFE AF: 0.285

Gnomad4 OTH AF: 0.276

Alfa AF: 0.153 Hom.: 284

Bravo AF: 0.268

Asia WGS AF: 0.297 AC: 1032 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	5.5
DANN	Benign	0.75

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: rs1048260; hg19: chr1-182542851;