dbSNP rs11072: RNASEL:c.*1196T>C (chr1-182574196-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.*1196T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 224,128 control chromosomes in the GnomAD database, including 9,032 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 0.27 ( 5969 hom., cov: 32)

Exomes 𝑓: 0.28 ( 3063 hom. )

Consequence

RNASEL
NM_021133.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.616

Publications

14 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=-0.97).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNASEL	NM_021133.4 link	c.*1196T>C		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.*1196T>C		3_prime_UTR_variant	Exon 7 of 7	1	NM_021133.4	ENSP00000356530.3		Q05823-1

Frequencies

GnomAD3 genomes

AF:

0.268

AC:

40762

AN:

152082

Hom.:

5965

Cov.:

show subpopulations

Gnomad AFR

AF:

0.192

Gnomad AMI

AF:

0.429

Gnomad AMR

AF:

0.357

Gnomad ASJ

AF:

0.427

Gnomad EAS

AF:

0.187

Gnomad SAS

AF:

0.386

Gnomad FIN

AF:

0.192

Gnomad MID

AF:

0.421

Gnomad NFE

AF:

0.292

Gnomad OTH

AF:

0.284

GnomAD4 exome

AF:

0.281

AC:

20203

AN:

71928

Hom.:

3063

Cov.:

AF XY:

0.285

AC XY:

9478

AN XY:

33208

show subpopulations

African (AFR)

AF:

0.199

AC:

671

AN:

3368

American (AMR)

AF:

0.339

AC:

732

AN:

2160

Ashkenazi Jewish (ASJ)

AF:

0.400

AC:

1829

AN:

4572

East Asian (EAS)

AF:

0.167

AC:

1702

AN:

10202

South Asian (SAS)

AF:

0.397

AC:

236

AN:

594

European-Finnish (FIN)

AF:

0.220

AC:

AN:

Middle Eastern (MID)

AF:

0.354

AC:

153

AN:

432

European-Non Finnish (NFE)

AF:

0.295

AC:

13135

AN:

44536

Other (OTH)

AF:

0.288

AC:

1734

AN:

6014

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

698

1395

2093

2790

3488

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

150

200

250

<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:

0.268

AC:

40778

AN:

152200

Hom.:

5969

Cov.:

AF XY:

0.268

AC XY:

19962

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.192

AC:

7978

AN:

41524

American (AMR)

AF:

0.357

AC:

5457

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.427

AC:

1480

AN:

3470

East Asian (EAS)

AF:

0.186

AC:

965

AN:

5178

South Asian (SAS)

AF:

0.386

AC:

1862

AN:

4826

European-Finnish (FIN)

AF:

0.192

AC:

2031

AN:

10594

Middle Eastern (MID)

AF:

0.432

AC:

127

AN:

294

European-Non Finnish (NFE)

AF:

0.292

AC:

19882

AN:

67998

Other (OTH)

AF:

0.286

AC:

605

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1523

3046

4569

6092

7615

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

414

828

1242

1656

2070

<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:

0.289

Hom.:

25153

Bravo

AF:

0.275

Asia WGS

AF:

0.301

AC:

1045

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.85

(source)

DANN

Benign

0.40

PhyloP100

-0.62

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