chr1-182585422-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 13/21 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

Publications

214 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 -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 VariationId 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 rank	MANE	Protein
RNASEL	NM_021133.4 link	c.1385G>A	p.Arg462Gln	missense_variant	Exon 2 of 7	ENST00000367559.7	NP_066956.1
RNASEL	XM_047427096.1 link	c.1385G>A	p.Arg462Gln	missense_variant	Exon 2 of 7		XP_047283052.1
RNASEL	XM_047427106.1 link	c.1385G>A	p.Arg462Gln	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.1385G>A	p.Arg462Gln	missense_variant	Exon 2 of 7	1	NM_021133.4	ENSP00000356530.3
RNASEL	ENST00000539397.1 link	c.1385G>A	p.Arg462Gln	missense_variant	Exon 2 of 6	2		ENSP00000440844.1

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

GnomAD2 exomes

AF:

0.305

AC:

76756

AN:

251298

AF XY:

0.315

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 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

African (AFR)

AF:

0.111

AC:

3730

AN:

33480

American (AMR)

AF:

0.179

AC:

7986

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.320

AC:

8351

AN:

26134

East Asian (EAS)

AF:

0.220

AC:

8722

AN:

39698

South Asian (SAS)

AF:

0.294

AC:

25371

AN:

86256

European-Finnish (FIN)

AF:

0.380

AC:

20289

AN:

53416

Middle Eastern (MID)

AF:

0.288

AC:

1660

AN:

5768

European-Non Finnish (NFE)

AF:

0.361

AC:

401686

AN:

1111980

Other (OTH)

AF:

0.320

AC:

19348

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

19438

38876

58314

77752

97190

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12364

24728

37092

49456

61820

<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:

0.282

AC:

42892

AN:

152002

Hom.:

6971

Cov.:

AF XY:

0.282

AC XY:

20959

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.123

AC:

5095

AN:

41496

American (AMR)

AF:

0.251

AC:

3827

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.305

AC:

1058

AN:

3472

East Asian (EAS)

AF:

0.235

AC:

1214

AN:

5156

South Asian (SAS)

AF:

0.292

AC:

1405

AN:

4812

European-Finnish (FIN)

AF:

0.384

AC:

4049

AN:

10534

Middle Eastern (MID)

AF:

0.310

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.371

AC:

25185

AN:

67952

Other (OTH)

AF:

0.301

AC:

635

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1477

2954

4430

5907

7384

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

442

884

1326

1768

2210

<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:

0.334

Hom.:

30228

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

Aug 17, 2022

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

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Hereditary cancer

Benign:1

Jan 23, 2024

Mendelics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Prostate cancer susceptibility

Other:1

Dec 01, 2002

OMIM

Significance:risk factor

Review Status:no assertion criteria provided

Collection Method:literature only

- -

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

(source)

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

PhyloP100

0.23

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

Mutation Taster

=98/2

polymorphism (auto)

(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