rs533259

Positions:

• chr1-182579884-A-G
• chr1-182579884-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.1905+1341T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.92 in 501,974 control chromosomes in the GnomAD database, including 213,447 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 0.89 (60482 hom., cov: 32)
  • Exomes 𝑓: 0.93 (152965 hom.)
• Consequence: RNASEL NM_021133.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.83

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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.933 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNASEL	NM_021133.4	c.1905+1341T>C		intron_variant		ENST00000367559.7
RNASEL	XM_047427096.1	c.1955+74T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNASEL	ENST00000367559.7	c.1905+1341T>C		intron_variant		1	NM_021133.4	P1
RNASEL	ENST00000539397.1	c.*70T>C		3_prime_UTR_variant	6/6	2

Frequencies

GnomAD3 genomes AF: 0.887 AC: 134883 AN: 152112 Hom.: 60446 Cov.: 32

Gnomad AFR AF: 0.739

Gnomad AMI AF: 0.966

Gnomad AMR AF: 0.945

Gnomad ASJ AF: 0.960

Gnomad EAS AF: 0.954

Gnomad SAS AF: 0.927

Gnomad FIN AF: 0.953

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.939

Gnomad OTH AF: 0.915

GnomAD4 exome AF: 0.934 AC: 326764 AN: 349744 Hom.: 152965 Cov.: 4 AF XY: 0.935 AC XY: 182860 AN XY: 195608

Gnomad4 AFR exome AF: 0.730

Gnomad4 AMR exome AF: 0.964

Gnomad4 ASJ exome AF: 0.958

Gnomad4 EAS exome AF: 0.958

Gnomad4 SAS exome AF: 0.933

Gnomad4 FIN exome AF: 0.950

Gnomad4 NFE exome AF: 0.937

Gnomad4 OTH exome AF: 0.931

GnomAD4 genome AF: 0.887 AC: 134977 AN: 152230 Hom.: 60482 Cov.: 32 AF XY: 0.889 AC XY: 66198 AN XY: 74444

Gnomad4 AFR AF: 0.739

Gnomad4 AMR AF: 0.945

Gnomad4 ASJ AF: 0.960

Gnomad4 EAS AF: 0.954

Gnomad4 SAS AF: 0.928

Gnomad4 FIN AF: 0.953

Gnomad4 NFE AF: 0.939

Gnomad4 OTH AF: 0.916

Alfa AF: 0.931 Hom.: 92465

Bravo AF: 0.878

Asia WGS AF: 0.939 AC: 3263 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.54
DANN	Benign	0.57

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: rs533259; hg19: chr1-182549019;