Genetic Variant RNASEL:c.1905+1341T>C (chr1-182579884-A-G) – 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.1905+1341T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.92 in 501,974 control chromosomes in the GnomAD database, including 213,447 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 0.89 ( 60482 hom., cov: 32)

Exomes 𝑓: 0.93 ( 152965 hom. )

Consequence

RNASEL
NM_021133.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.83

Publications

26 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=-0.99).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.933 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021133.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNASEL	NM_021133.4	MANE Select	c.1905+1341T>C		intron	N/A	NP_066956.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNASEL	ENST00000367559.7	TSL:1 MANE Select	c.1905+1341T>C		intron	N/A	ENSP00000356530.3
	RNASEL	ENST00000539397.1	TSL:2	c.*70T>C		3_prime_UTR	Exon 6 of 6	ENSP00000440844.1

Frequencies

GnomAD3 genomes

AF:

0.887

AC:

134883

AN:

152112

Hom.:

60446

Cov.:

show subpopulations

Gnomad AFR

AF:

0.739

Gnomad AMI

AF:

0.966

Gnomad AMR

AF:

0.945

Gnomad ASJ

AF:

0.960

Gnomad EAS

AF:

0.954

Gnomad SAS

AF:

0.927

Gnomad FIN

AF:

0.953

Gnomad MID

AF:

0.962

Gnomad NFE

AF:

0.939

Gnomad OTH

AF:

0.915

GnomAD4 exome

AF:

0.934

AC:

326764

AN:

349744

Hom.:

152965

Cov.:

AF XY:

0.935

AC XY:

182860

AN XY:

195608

show subpopulations

African (AFR)

AF:

0.730

AC:

6871

AN:

9412

American (AMR)

AF:

0.964

AC:

26354

AN:

27336

Ashkenazi Jewish (ASJ)

AF:

0.958

AC:

10603

AN:

11064

East Asian (EAS)

AF:

0.958

AC:

9021

AN:

9420

South Asian (SAS)

AF:

0.933

AC:

56540

AN:

60590

European-Finnish (FIN)

AF:

0.950

AC:

12163

AN:

12802

Middle Eastern (MID)

AF:

0.941

AC:

2719

AN:

2888

European-Non Finnish (NFE)

AF:

0.937

AC:

187897

AN:

200558

Other (OTH)

AF:

0.931

AC:

14596

AN:

15674

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1230

2459

3689

4918

6148

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1678

3356

5034

6712

8390

<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:

0.887

AC:

134977

AN:

152230

Hom.:

60482

Cov.:

AF XY:

0.889

AC XY:

66198

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.739

AC:

30677

AN:

41486

American (AMR)

AF:

0.945

AC:

14450

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.960

AC:

3330

AN:

3470

East Asian (EAS)

AF:

0.954

AC:

4938

AN:

5178

South Asian (SAS)

AF:

0.928

AC:

4482

AN:

4830

European-Finnish (FIN)

AF:

0.953

AC:

10125

AN:

10622

Middle Eastern (MID)

AF:

0.959

AC:

282

AN:

294

European-Non Finnish (NFE)

AF:

0.939

AC:

63881

AN:

68034

Other (OTH)

AF:

0.916

AC:

1931

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

720

1440

2159

2879

3599

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

896

1792

2688

3584

4480

<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:

0.921

Hom.:

211930

Bravo

AF:

0.878

Asia WGS

AF:

0.939

AC:

3263

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.54

(source)

DANN

Benign

0.57

PhyloP100

-1.8

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over