rs12742422

Positions:

• chr1-182585268-T-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_021133.4(RNASEL):​c.1480+59A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0115 in 1,558,776 control chromosomes in the GnomAD database, including 144 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 0.0084 (9 hom., cov: 32)
  • Exomes 𝑓: 0.012 (135 hom.)
• Consequence: RNASEL NM_021133.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.498

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BS2: High AC in GnomAd4 at 1277 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNASEL	NM_021133.4	c.1480+59A>G		intron_variant		ENST00000367559.7	NP_066956.1
RNASEL	XM_047427096.1	c.1480+59A>G		intron_variant			XP_047283052.1
RNASEL	XM_047427106.1	c.1480+59A>G		intron_variant			XP_047283062.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNASEL	ENST00000367559.7	c.1480+59A>G		intron_variant		1	NM_021133.4	ENSP00000356530	P1
RNASEL	ENST00000539397.1	c.1480+59A>G		intron_variant		2		ENSP00000440844

Frequencies

GnomAD3 genomes AF: 0.00840 AC: 1278 AN: 152192 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.00212

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.00753

Gnomad ASJ AF: 0.00577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00580

Gnomad FIN AF: 0.0105

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0131

Gnomad OTH AF: 0.00716

GnomAD4 exome AF: 0.0118 AC: 16651 AN: 1406466 Hom.: 135 AF XY: 0.0117 AC XY: 8173 AN XY: 699578

Gnomad4 AFR exome AF: 0.00141

Gnomad4 AMR exome AF: 0.00574

Gnomad4 ASJ exome AF: 0.00492

Gnomad4 EAS exome AF: 0.0000255

Gnomad4 SAS exome AF: 0.00884

Gnomad4 FIN exome AF: 0.0112

Gnomad4 NFE exome AF: 0.0133

Gnomad4 OTH exome AF: 0.0112

GnomAD4 genome AF: 0.00838 AC: 1277 AN: 152310 Hom.: 9 Cov.: 32 AF XY: 0.00828 AC XY: 617 AN XY: 74490

Gnomad4 AFR AF: 0.00212

Gnomad4 AMR AF: 0.00752

Gnomad4 ASJ AF: 0.00577

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00559

Gnomad4 FIN AF: 0.0105

Gnomad4 NFE AF: 0.0131

Gnomad4 OTH AF: 0.00709

Alfa AF: 0.0118 Hom.: 2

Bravo AF: 0.00778

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.8
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: rs12742422; hg19: chr1-182554403;