chr1-182575680-T-C

Position:

• chr1-182575680-T-C

Variant summary

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

The ENST00000367559.7(RNASEL):​c.2040-102A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 1,444,020 control chromosomes in the GnomAD database, including 76,054 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 0.29 (6905 hom., cov: 32)
  • Exomes 𝑓: 0.32 (69149 hom.)
• Consequence: RNASEL ENST00000367559.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.108

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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNASEL	NM_021133.4	c.2040-102A>G		intron_variant		ENST00000367559.7	NP_066956.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNASEL	ENST00000367559.7	c.2040-102A>G		intron_variant		1	NM_021133.4	ENSP00000356530	P1

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43934 AN: 152114 Hom.: 6902 Cov.: 32

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.449

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.466

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.319

GnomAD4 exome AF: 0.322 AC: 416026 AN: 1291788 Hom.: 69149 AF XY: 0.325 AC XY: 209768 AN XY: 645188

Gnomad4 AFR exome AF: 0.200

Gnomad4 AMR exome AF: 0.302

Gnomad4 ASJ exome AF: 0.446

Gnomad4 EAS exome AF: 0.179

Gnomad4 SAS exome AF: 0.393

Gnomad4 FIN exome AF: 0.281

Gnomad4 NFE exome AF: 0.324

Gnomad4 OTH exome AF: 0.326

GnomAD4 genome AF: 0.289 AC: 43942 AN: 152232 Hom.: 6905 Cov.: 32 AF XY: 0.291 AC XY: 21623 AN XY: 74420

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.344

Gnomad4 ASJ AF: 0.466

Gnomad4 EAS AF: 0.188

Gnomad4 SAS AF: 0.400

Gnomad4 FIN AF: 0.265

Gnomad4 NFE AF: 0.320

Gnomad4 OTH AF: 0.321

Alfa AF: 0.295 Hom.: 3568

Bravo AF: 0.287

Asia WGS AF: 0.313 AC: 1089 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.1
DANN	Benign	0.49

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: rs11807829; hg19: chr1-182544815;