Genetic Variant RNASEL:c.*1676C>G (chr1-182573716-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_021133.4(RNASEL):c.*1676C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 182,562 control chromosomes in the GnomAD database, including 6,760 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 0.26 ( 5633 hom., cov: 33)

Exomes 𝑓: 0.26 ( 1127 hom. )

Consequence

RNASEL
NM_021133.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0980

Publications

12 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNASEL	NM_021133.4 link	c.*1676C>G		3_prime_UTR_variant	Exon 7 of 7	ENST00000367559.7	NP_066956.1	Q05823-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNASEL	ENST00000367559.7 link	c.*1676C>G		3_prime_UTR_variant	Exon 7 of 7	1	NM_021133.4	ENSP00000356530.3		Q05823-1

Frequencies

GnomAD3 genomes

AF:

0.262

AC:

39778

AN:

152040

Hom.:

5629

Cov.:

show subpopulations

Gnomad AFR

AF:

0.191

Gnomad AMI

AF:

0.427

Gnomad AMR

AF:

0.345

Gnomad ASJ

AF:

0.374

Gnomad EAS

AF:

0.186

Gnomad SAS

AF:

0.382

Gnomad FIN

AF:

0.192

Gnomad MID

AF:

0.411

Gnomad NFE

AF:

0.285

Gnomad OTH

AF:

0.273

GnomAD4 exome

AF:

0.265

AC:

8045

AN:

30404

Hom.:

1127

Cov.:

AF XY:

0.270

AC XY:

3788

AN XY:

14010

show subpopulations

African (AFR)

AF:

0.187

AC:

205

AN:

1094

American (AMR)

AF:

0.315

AC:

227

AN:

720

Ashkenazi Jewish (ASJ)

AF:

0.354

AC:

691

AN:

1952

East Asian (EAS)

AF:

0.171

AC:

1018

AN:

5950

South Asian (SAS)

AF:

0.372

AC:

AN:

266

European-Finnish (FIN)

AF:

0.357

AC:

AN:

Middle Eastern (MID)

AF:

0.354

AC:

AN:

192

European-Non Finnish (NFE)

AF:

0.284

AC:

5040

AN:

17776

Other (OTH)

AF:

0.284

AC:

692

AN:

2440

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

258

517

775

1034

1292

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<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:

0.262

AC:

39794

AN:

152158

Hom.:

5633

Cov.:

AF XY:

0.262

AC XY:

19474

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.191

AC:

7927

AN:

41498

American (AMR)

AF:

0.345

AC:

5279

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.374

AC:

1298

AN:

3466

East Asian (EAS)

AF:

0.185

AC:

958

AN:

5178

South Asian (SAS)

AF:

0.382

AC:

1841

AN:

4822

European-Finnish (FIN)

AF:

0.192

AC:

2033

AN:

10602

Middle Eastern (MID)

AF:

0.422

AC:

124

AN:

294

European-Non Finnish (NFE)

AF:

0.285

AC:

19362

AN:

67980

Other (OTH)

AF:

0.276

AC:

583

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1526

3051

4577

6102

7628

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

408

816

1224

1632

2040

<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:

0.153

Hom.:

284

Bravo

AF:

0.268

Asia WGS

AF:

0.297

AC:

1032

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

5.5

(source)

DANN

Benign

0.75

PhyloP100

0.098

Mutation Taster

=100/0

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

Computational scores

Splicing

Publications

Other links and lift over