1-182580201-A-G

Variant summary

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

The NM_021133.4(RNASEL):c.1905+1024T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 152,120 control chromosomes in the GnomAD database, including 8,627 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 0.33 (8627 hom., cov: 33)
• Consequence: RNASEL NM_021133.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0580

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNASEL	NM_021133.4	c.1905+1024T>C		intron_variant		ENST00000367559.7
RNASEL	XM_047427096.1	c.1906-194T>C		intron_variant
RNASEL	XM_047427106.1	c.1906-194T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNASEL	ENST00000367559.7	c.1905+1024T>C		intron_variant		1	NM_021133.4	P1
RNASEL	ENST00000539397.1	c.1906-194T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50752 AN: 152002 Hom.: 8625 Cov.: 33

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.335

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.334 AC: 50779 AN: 152120 Hom.: 8627 Cov.: 33 AF XY: 0.332 AC XY: 24692 AN XY: 74366

Gnomad4 AFR AF: 0.303

Gnomad4 AMR AF: 0.274

Gnomad4 ASJ AF: 0.313

Gnomad4 EAS AF: 0.242

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.377

Gnomad4 NFE AF: 0.371

Gnomad4 OTH AF: 0.336

Alfa AF: 0.270 Hom.: 1029

Bravo AF: 0.321

Asia WGS AF: 0.294 AC: 1026 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.45
Dann	Benign	0.54

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: rs579006; hg19: chr1-182549336;