rs486907

chr1-182585422-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_021133.4(RNASEL):c.1385G>A(p.Arg462Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 1,613,854 control chromosomes in the GnomAD database, including 94,567 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.28 (6971 hom., cov: 32)
  • Exomes 𝑓: 0.34 (87596 hom.)
• Consequence: RNASEL NM_021133.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter U:1 B:1 O:1
• Conservation: PhyloP100: 0.229

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0041000247).
• BP6: Variant 1-182585422-C-T is Benign according to our data. Variant chr1-182585422-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 13006.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNASEL	NM_021133.4	c.1385G>A	p.Arg462Gln	missense_variant	2/7	ENST00000367559.7
RNASEL	XM_047427096.1	c.1385G>A	p.Arg462Gln	missense_variant	2/7
RNASEL	XM_047427106.1	c.1385G>A	p.Arg462Gln	missense_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNASEL	ENST00000367559.7	c.1385G>A	p.Arg462Gln	missense_variant	2/7	1	NM_021133.4	P1
RNASEL	ENST00000539397.1	c.1385G>A	p.Arg462Gln	missense_variant	2/6	2

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42890 AN: 151884 Hom.: 6974 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.300

GnomAD3 exomes AF: 0.305 AC: 76756 AN: 251298 Hom.: 12737 AF XY: 0.315 AC XY: 42765 AN XY: 135806

Gnomad AFR exome AF: 0.123

Gnomad AMR exome AF: 0.172

Gnomad ASJ exome AF: 0.319

Gnomad EAS exome AF: 0.233

Gnomad SAS exome AF: 0.297

Gnomad FIN exome AF: 0.384

Gnomad NFE exome AF: 0.369

Gnomad OTH exome AF: 0.330

GnomAD4 exome AF: 0.340 AC: 497143 AN: 1461852 Hom.: 87596 Cov.: 45 AF XY: 0.340 AC XY: 247265 AN XY: 727232

Gnomad4 AFR exome AF: 0.111

Gnomad4 AMR exome AF: 0.179

Gnomad4 ASJ exome AF: 0.320

Gnomad4 EAS exome AF: 0.220

Gnomad4 SAS exome AF: 0.294

Gnomad4 FIN exome AF: 0.380

Gnomad4 NFE exome AF: 0.361

Gnomad4 OTH exome AF: 0.320

GnomAD4 genome AF: 0.282 AC: 42892 AN: 152002 Hom.: 6971 Cov.: 32 AF XY: 0.282 AC XY: 20959 AN XY: 74290

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.251

Gnomad4 ASJ AF: 0.305

Gnomad4 EAS AF: 0.235

Gnomad4 SAS AF: 0.292

Gnomad4 FIN AF: 0.384

Gnomad4 NFE AF: 0.371

Gnomad4 OTH AF: 0.301

Alfa AF: 0.348 Hom.: 23401

Bravo AF: 0.262

TwinsUK AF: 0.358 AC: 1326

ALSPAC AF: 0.348 AC: 1341

ESP6500AA AF: 0.133 AC: 587

ESP6500EA AF: 0.356 AC: 3065

ExAC AF: 0.309 AC: 37496

Asia WGS AF: 0.283 AC: 986 AN: 3478

EpiCase AF: 0.362

EpiControl AF: 0.366

ClinVar

Significance: Likely benign

Submissions summary: Uncertain:1 Benign:1 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

Prostate cancer, hereditary, 1 Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Laboratory of Virology, Oncology, Biosciences and Environment, Faculty of Sciences and Techniques, Mohammedia- University Hassan II of Casablanca

Aug 17, 2022

- -

Hereditary cancer Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Mendelics

Jan 23, 2024

- -

Prostate cancer, susceptibility to Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Dec 01, 2002

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.61
Cadd	Benign	18
Dann	Uncertain	1.0
DEOGEN2	Benign	0.061	T;.
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.65	T;T
MetaRNN	Benign	0.0041	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.3	M;M
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.074
Sift	Benign	0.030	D;D
Sift4G	Uncertain	0.043	D;T
Polyphen		1.0	D;.
Vest4		0.071
MPC		0.12
ClinPred		0.016	T
GERP RS		0.056
Varity_R		0.10
gMVP		0.23

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: rs486907; hg19: chr1-182554557; COSMIC: COSV62376340;