chr1-182586518-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_021133.4(RNASEL):c.289A>C(p.Ile97Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00905 in 1,610,920 control chromosomes in the GnomAD database, including 92 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0055 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0094 ( 87 hom. )

Consequence

RNASEL
NM_021133.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.56

Publications

24 publications found

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 Gene-Disease associations (from GenCC):

prostate cancer, hereditary, 1
Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

RNASEL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00963223).

BP6

Variant 1-182586518-T-G is Benign according to our data. Variant chr1-182586518-T-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 806296.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 834 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNASEL	NM_021133.4 link	c.289A>C	p.Ile97Leu	missense_variant	Exon 2 of 7	ENST00000367559.7	NP_066956.1	Q05823-1
RNASEL	XM_047427096.1 link	c.289A>C	p.Ile97Leu	missense_variant	Exon 2 of 7		XP_047283052.1
RNASEL	XM_047427106.1 link	c.289A>C	p.Ile97Leu	missense_variant	Exon 2 of 6		XP_047283062.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNASEL	ENST00000367559.7 link	c.289A>C	p.Ile97Leu	missense_variant	Exon 2 of 7	1	NM_021133.4	ENSP00000356530.3		Q05823-1
RNASEL	ENST00000539397.1 link	c.289A>C	p.Ile97Leu	missense_variant	Exon 2 of 6	2		ENSP00000440844.1		Q05823-2

Frequencies

GnomAD3 genomes

AF:

0.00548

AC:

834

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00171

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00499

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00985

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.00663

AC:

1659

AN:

250096

AF XY:

0.00689

show subpopulations

Gnomad AFR exome

AF:

0.00166

Gnomad AMR exome

AF:

0.00160

Gnomad ASJ exome

AF:

0.000200

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00658

Gnomad NFE exome

AF:

0.0117

Gnomad OTH exome

AF:

0.00625

GnomAD4 exome

AF:

0.00943

AC:

13748

AN:

1458568

Hom.:

Cov.:

AF XY:

0.00924

AC XY:

6696

AN XY:

725038

show subpopulations

African (AFR)

AF:

0.00159

AC:

AN:

33266

American (AMR)

AF:

0.00196

AC:

AN:

44446

Ashkenazi Jewish (ASJ)

AF:

0.000268

AC:

AN:

26092

East Asian (EAS)

AF:

0.00

AC:

AN:

39624

South Asian (SAS)

AF:

0.00247

AC:

213

AN:

86162

European-Finnish (FIN)

AF:

0.00678

AC:

362

AN:

53384

Middle Eastern (MID)

AF:

0.000521

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.0114

AC:

12645

AN:

1109602

Other (OTH)

AF:

0.00628

AC:

378

AN:

60238

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

856

1713

2569

3426

4282

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

470

940

1410

1880

2350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00547

AC:

834

AN:

152352

Hom.:

Cov.:

AF XY:

0.00523

AC XY:

390

AN XY:

74506

show subpopulations

African (AFR)

AF:

0.00171

AC:

AN:

41588

American (AMR)

AF:

0.00163

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00499

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00985

AC:

670

AN:

68034

Other (OTH)

AF:

0.00236

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

130

173

216

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00854

Hom.:

Bravo

AF:

0.00517

TwinsUK

AF:

0.0129

AC:

ALSPAC

AF:

0.0143

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.00919

AC:

ExAC

AF:

0.00769

AC:

934

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00823

EpiControl

AF:

0.00848

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Apr 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

RNASEL: BS1, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.048

T;.

Eigen

Benign

0.030

Eigen_PC

Benign

0.033

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.83

T;T

MetaRNN

Benign

0.0096

T;T

MetaSVM

Benign

-0.85

MutationAssessor

Benign

0.51

N;N

PhyloP100

1.6

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.66

N;N

REVEL

Uncertain

0.30

Sift

Benign

0.033

D;D

Sift4G

Benign

0.21

T;T

Polyphen

1.0

D;.

Vest4

0.35

MVP

0.76

MPC

0.12

ClinPred

0.033

GERP RS

4.7

Varity_R

0.31

gMVP

0.44

Mutation Taster

=92/8

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over