dbSNP rs12742422: RNASEL:c.1480+59A>G (chr1-182585268-T-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_021133.4(RNASEL):c.1480+59A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0115 in 1,558,776 control chromosomes in the GnomAD database, including 144 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 0.0084 ( 9 hom., cov: 32)

Exomes 𝑓: 0.012 ( 135 hom. )

Consequence

RNASEL
NM_021133.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.498

Publications

1 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 -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BS2

High AC in GnomAd4 at 1277 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNASEL	NM_021133.4	MANE Select	c.1480+59A>G		intron	N/A	NP_066956.1	Q05823-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RNASEL	ENST00000367559.7	TSL:1 MANE Select	c.1480+59A>G	intron	N/A	ENSP00000356530.3	Q05823-1
RNASEL	ENST00000946546.1		c.1480+59A>G	intron	N/A	ENSP00000616605.1
RNASEL	ENST00000890859.1		c.1480+59A>G	intron	N/A	ENSP00000560918.1

Frequencies

GnomAD3 genomes

AF:

0.00840

AC:

1278

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00212

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.00753

Gnomad ASJ

AF:

0.00577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00580

Gnomad FIN

AF:

0.0105

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0131

Gnomad OTH

AF:

0.00716

GnomAD4 exome

AF:

0.0118

AC:

16651

AN:

1406466

Hom.:

135

AF XY:

0.0117

AC XY:

8173

AN XY:

699578

show subpopulations

African (AFR)

AF:

0.00141

AC:

AN:

31832

American (AMR)

AF:

0.00574

AC:

235

AN:

40970

Ashkenazi Jewish (ASJ)

AF:

0.00492

AC:

120

AN:

24380

East Asian (EAS)

AF:

0.0000255

AC:

AN:

39250

South Asian (SAS)

AF:

0.00884

AC:

718

AN:

81250

European-Finnish (FIN)

AF:

0.0112

AC:

592

AN:

52690

Middle Eastern (MID)

AF:

0.00646

AC:

AN:

5576

European-Non Finnish (NFE)

AF:

0.0133

AC:

14250

AN:

1072190

Other (OTH)

AF:

0.0112

AC:

654

AN:

58328

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

821

1642

2463

3284

4105

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

538

1076

1614

2152

2690

<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:

0.00838

AC:

1277

AN:

152310

Hom.:

Cov.:

AF XY:

0.00828

AC XY:

617

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.00212

AC:

AN:

41578

American (AMR)

AF:

0.00752

AC:

115

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00577

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00559

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0105

AC:

112

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0131

AC:

888

AN:

68024

Other (OTH)

AF:

0.00709

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

133

200

266

333

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0110

Hom.:

Bravo

AF:

0.00778

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.8

(source)

DANN

Benign

0.77

PhyloP100

0.50

Mutation Taster

=100/0

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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