Genetic Variant RNASEL:c.2040-102A>G (chr1-182575680-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.2040-102A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 1,444,020 control chromosomes in the GnomAD database, including 76,054 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 0.29 ( 6905 hom., cov: 32)

Exomes 𝑓: 0.32 ( 69149 hom. )

Consequence

RNASEL
NM_021133.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.108

Publications

18 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=-0.83).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNASEL	NM_021133.4 link	c.2040-102A>G		intron_variant	Intron 6 of 6	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.2040-102A>G		intron_variant	Intron 6 of 6	1	NM_021133.4	ENSP00000356530.3		Q05823-1

Frequencies

GnomAD3 genomes

AF:

0.289

AC:

43934

AN:

152114

Hom.:

6902

Cov.:

show subpopulations

Gnomad AFR

AF:

0.200

Gnomad AMI

AF:

0.449

Gnomad AMR

AF:

0.345

Gnomad ASJ

AF:

0.466

Gnomad EAS

AF:

0.188

Gnomad SAS

AF:

0.400

Gnomad FIN

AF:

0.265

Gnomad MID

AF:

0.472

Gnomad NFE

AF:

0.321

Gnomad OTH

AF:

0.319

GnomAD4 exome

AF:

0.322

AC:

416026

AN:

1291788

Hom.:

69149

AF XY:

0.325

AC XY:

209768

AN XY:

645188

show subpopulations

African (AFR)

AF:

0.200

AC:

5944

AN:

29686

American (AMR)

AF:

0.302

AC:

11095

AN:

36724

Ashkenazi Jewish (ASJ)

AF:

0.446

AC:

11034

AN:

24732

East Asian (EAS)

AF:

0.179

AC:

6430

AN:

36004

South Asian (SAS)

AF:

0.393

AC:

30851

AN:

78422

European-Finnish (FIN)

AF:

0.281

AC:

11373

AN:

40488

Middle Eastern (MID)

AF:

0.401

AC:

2157

AN:

5374

European-Non Finnish (NFE)

AF:

0.324

AC:

319316

AN:

985746

Other (OTH)

AF:

0.326

AC:

17826

AN:

54612

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

14264

28528

42792

57056

71320

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10144

20288

30432

40576

50720

<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:

0.289

AC:

43942

AN:

152232

Hom.:

6905

Cov.:

AF XY:

0.291

AC XY:

21623

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.200

AC:

8327

AN:

41546

American (AMR)

AF:

0.344

AC:

5269

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.466

AC:

1616

AN:

3470

East Asian (EAS)

AF:

0.188

AC:

972

AN:

5184

South Asian (SAS)

AF:

0.400

AC:

1930

AN:

4822

European-Finnish (FIN)

AF:

0.265

AC:

2810

AN:

10600

Middle Eastern (MID)

AF:

0.473

AC:

139

AN:

294

European-Non Finnish (NFE)

AF:

0.320

AC:

21791

AN:

67994

Other (OTH)

AF:

0.321

AC:

679

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1555

3110

4665

6220

7775

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

440

880

1320

1760

2200

<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:

0.299

Hom.:

3991

Bravo

AF:

0.287

Asia WGS

AF:

0.313

AC:

1089

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.1

(source)

DANN

Benign

0.49

PhyloP100

-0.11

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