Variant rs486907 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

Clinical Significance

Likely benign criteria provided, single submitter U:1B:1O:1

Conservation

PhyloP100: 0.229

Variant links:

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]

RNASEL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Protein
RNASEL	NM_021133.4 linkuse as main transcript	c.1385G>A	p.Arg462Gln	missense_variant	2/7	ENST00000367559.7	NP_066956.1
RNASEL	XM_047427096.1 linkuse as main transcript	c.1385G>A	p.Arg462Gln	missense_variant	2/7		XP_047283052.1
RNASEL	XM_047427106.1 linkuse as main transcript	c.1385G>A	p.Arg462Gln	missense_variant	2/6		XP_047283062.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNASEL	ENST00000367559.7 linkuse as main transcript	c.1385G>A	p.Arg462Gln	missense_variant	2/7	1	NM_021133.4	ENSP00000356530	P1	Q05823-1
RNASEL	ENST00000539397.1 linkuse as main transcript	c.1385G>A	p.Arg462Gln	missense_variant	2/6	2		ENSP00000440844		Q05823-2

Frequencies

GnomAD3 genomes

AF:

0.282

AC:

42890

AN:

151884

Hom.:

6974

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.340

AC XY:

247265

AN XY:

727232

show subpopulations

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.:

AF XY:

0.282

AC XY:

20959

AN XY:

74290

show subpopulations

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:1Benign:1Other:1

Revision: criteria provided, single submitter

LINK: link

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

- -

RECLASSIFIED - CDH1 POLYMORPHISM

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

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.061

T;.

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.65

T;T

MetaRNN

Benign

0.0041

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.3

M;M

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.22

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over