rs533259

Variant names:

• chr1-182579884-A-C
• NM_021133.4:c.1905+1341T>G

Your query was ambiguous. Multiple possible variants found:

• chr1-182579884-A-C
• chr1-182579884-A-G
• chr1-182579884-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021133.4(RNASEL):​c.1905+1341T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000286 in 349,816 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000029 (0 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNASEL	NM_021133.4	c.1905+1341T>G		intron_variant	Intron 5 of 6	ENST00000367559.7	NP_066956.1
RNASEL	XM_047427096.1	c.1955+74T>G		intron_variant	Intron 6 of 6		XP_047283052.1
RNASEL	XM_047427106.1	c.*70T>G		downstream_gene_variant			XP_047283062.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNASEL	ENST00000367559.7	c.1905+1341T>G		intron_variant	Intron 5 of 6	1	NM_021133.4	ENSP00000356530.3
RNASEL	ENST00000539397	c.*70T>G		3_prime_UTR_variant	Exon 6 of 6	2		ENSP00000440844.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000286 AC: 1 AN: 349816 Hom.: 0 Cov.: 4 AF XY: 0.00 AC XY: 0 AN XY: 195644

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000781

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.52
DANN	Benign	0.58

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-182549019;