dbSNP rs12135247: RNASEL:c.*590A>G (chr1-182574802-T-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.*590A>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 0.269 in 231,212 control chromosomes in the GnomAD database, including 9,013 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 ( 5627 hom., cov: 29)

Exomes 𝑓: 0.28 ( 3386 hom. )

Consequence

RNASEL
NM_021133.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.44

Publications

7 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=-0.9).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNASEL	NM_021133.4 link	c.*590A>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.*590A>G		3_prime_UTR_variant	Exon 7 of 7	1	NM_021133.4	ENSP00000356530.3		Q05823-1

Frequencies

GnomAD3 genomes

AF:

0.263

AC:

39432

AN:

150044

Hom.:

5625

Cov.:

show subpopulations

Gnomad AFR

AF:

0.192

Gnomad AMI

AF:

0.427

Gnomad AMR

AF:

0.324

Gnomad ASJ

AF:

0.425

Gnomad EAS

AF:

0.187

Gnomad SAS

AF:

0.376

Gnomad FIN

AF:

0.192

Gnomad MID

AF:

0.421

Gnomad NFE

AF:

0.289

Gnomad OTH

AF:

0.277

GnomAD4 exome

AF:

0.280

AC:

22670

AN:

81050

Hom.:

3386

Cov.:

AF XY:

0.284

AC XY:

10598

AN XY:

37316

show subpopulations

African (AFR)

AF:

0.203

AC:

785

AN:

3864

American (AMR)

AF:

0.284

AC:

747

AN:

2626

Ashkenazi Jewish (ASJ)

AF:

0.403

AC:

2043

AN:

5064

East Asian (EAS)

AF:

0.169

AC:

1911

AN:

11294

South Asian (SAS)

AF:

0.394

AC:

291

AN:

738

European-Finnish (FIN)

AF:

0.210

AC:

AN:

Middle Eastern (MID)

AF:

0.360

AC:

174

AN:

484

European-Non Finnish (NFE)

AF:

0.294

AC:

14772

AN:

50208

Other (OTH)

AF:

0.288

AC:

1934

AN:

6710

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

820

1640

2461

3281

4101

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

116

174

232

290

<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:

0.263

AC:

39441

AN:

150162

Hom.:

5627

Cov.:

AF XY:

0.263

AC XY:

19215

AN XY:

73158

show subpopulations

African (AFR)

AF:

0.192

AC:

7842

AN:

40820

American (AMR)

AF:

0.323

AC:

4803

AN:

14884

Ashkenazi Jewish (ASJ)

AF:

0.425

AC:

1469

AN:

3456

East Asian (EAS)

AF:

0.186

AC:

955

AN:

5126

South Asian (SAS)

AF:

0.376

AC:

1753

AN:

4666

European-Finnish (FIN)

AF:

0.192

AC:

1968

AN:

10276

Middle Eastern (MID)

AF:

0.432

AC:

127

AN:

294

European-Non Finnish (NFE)

AF:

0.289

AC:

19558

AN:

67662

Other (OTH)

AF:

0.279

AC:

579

AN:

2072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1380

2759

4139

5518

6898

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

402

804

1206

1608

2010

<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:

0.273

Hom.:

3539

Bravo

AF:

0.267

Asia WGS

AF:

0.298

AC:

1037

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.54

(source)

DANN

Benign

0.54

PhyloP100

-1.4

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