rs11072

chr1-182574196-A-Gchr1-182574196-A-T

Variant summary

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

The NM_021133.4(RNASEL):c.*1196T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 224,128 control chromosomes in the GnomAD database, including 9,032 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 0.27 (5969 hom., cov: 32)
  • Exomes 𝑓: 0.28 (3063 hom.)
• Consequence: RNASEL NM_021133.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.616

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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNASEL	NM_021133.4	c.*1196T>C		3_prime_UTR_variant	7/7	ENST00000367559.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNASEL	ENST00000367559.7	c.*1196T>C		3_prime_UTR_variant	7/7	1	NM_021133.4	P1

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40762 AN: 152082 Hom.: 5965 Cov.: 32

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.357

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.284

GnomAD4 exome AF: 0.281 AC: 20203 AN: 71928 Hom.: 3063 Cov.: 0 AF XY: 0.285 AC XY: 9478 AN XY: 33208

Gnomad4 AFR exome AF: 0.199

Gnomad4 AMR exome AF: 0.339

Gnomad4 ASJ exome AF: 0.400

Gnomad4 EAS exome AF: 0.167

Gnomad4 SAS exome AF: 0.397

Gnomad4 FIN exome AF: 0.220

Gnomad4 NFE exome AF: 0.295

Gnomad4 OTH exome AF: 0.288

GnomAD4 genome AF: 0.268 AC: 40778 AN: 152200 Hom.: 5969 Cov.: 32 AF XY: 0.268 AC XY: 19962 AN XY: 74416

Gnomad4 AFR AF: 0.192

Gnomad4 AMR AF: 0.357

Gnomad4 ASJ AF: 0.427

Gnomad4 EAS AF: 0.186

Gnomad4 SAS AF: 0.386

Gnomad4 FIN AF: 0.192

Gnomad4 NFE AF: 0.292

Gnomad4 OTH AF: 0.286

Alfa AF: 0.297 Hom.: 11514

Bravo AF: 0.275

Asia WGS AF: 0.301 AC: 1045 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.85
Dann	Benign	0.40

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: rs11072; hg19: chr1-182543331;