Genetic Variant RNASEL:c.*1676C>G (chr1-182573716-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is . The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_021133.4(RNASEL):c.*1676C>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 0.262 in 182,562 control chromosomes in the GnomAD database, including 6,760 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 ( 5633 hom., cov: 33)

Exomes 𝑓: 0.26 ( 1127 hom. )

Consequence

RNASEL
NM_021133.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0980

Publications

12 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):

multisystem inflammatory syndrome in children and adults
Inheritance: AR Classification: MODERATE Submitted by: PanelApp Australia
prostate cancer, hereditary, 1
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

RNASEL links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_021133.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.86).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.367 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNASEL	NM_021133.4	MANE Select	c.*1676C>G		3_prime_UTR	Exon 7 of 7	NP_066956.1	Q05823-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RNASEL	ENST00000367559.7	TSL:1 MANE Select	c.*1676C>G	3_prime_UTR	Exon 7 of 7	ENSP00000356530.3	Q05823-1
RNASEL	ENST00000946546.1		c.*1676C>G	3_prime_UTR	Exon 7 of 7	ENSP00000616605.1
RNASEL	ENST00000890859.1		c.*1676C>G	3_prime_UTR	Exon 7 of 7	ENSP00000560918.1

Frequencies

GnomAD3 genomes

AF:

0.262

AC:

39778

AN:

152040

Hom.:

5629

Cov.:

show subpopulations

Gnomad AFR

AF:

0.191

Gnomad AMI

AF:

0.427

Gnomad AMR

AF:

0.345

Gnomad ASJ

AF:

0.374

Gnomad EAS

AF:

0.186

Gnomad SAS

AF:

0.382

Gnomad FIN

AF:

0.192

Gnomad MID

AF:

0.411

Gnomad NFE

AF:

0.285

Gnomad OTH

AF:

0.273

GnomAD4 exome

AF:

0.265

AC:

8045

AN:

30404

Hom.:

1127

Cov.:

AF XY:

0.270

AC XY:

3788

AN XY:

14010

show subpopulations

African (AFR)

AF:

0.187

AC:

205

AN:

1094

American (AMR)

AF:

0.315

AC:

227

AN:

720

Ashkenazi Jewish (ASJ)

AF:

0.354

AC:

691

AN:

1952

East Asian (EAS)

AF:

0.171

AC:

1018

AN:

5950

South Asian (SAS)

AF:

0.372

AC:

AN:

266

European-Finnish (FIN)

AF:

0.357

AC:

AN:

Middle Eastern (MID)

AF:

0.354

AC:

AN:

192

European-Non Finnish (NFE)

AF:

0.284

AC:

5040

AN:

17776

Other (OTH)

AF:

0.284

AC:

692

AN:

2440

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

258

517

775

1034

1292

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<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:

0.262

AC:

39794

AN:

152158

Hom.:

5633

Cov.:

AF XY:

0.262

AC XY:

19474

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.191

AC:

7927

AN:

41498

American (AMR)

AF:

0.345

AC:

5279

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.374

AC:

1298

AN:

3466

East Asian (EAS)

AF:

0.185

AC:

958

AN:

5178

South Asian (SAS)

AF:

0.382

AC:

1841

AN:

4822

European-Finnish (FIN)

AF:

0.192

AC:

2033

AN:

10602

Middle Eastern (MID)

AF:

0.422

AC:

124

AN:

294

European-Non Finnish (NFE)

AF:

0.285

AC:

19362

AN:

67980

Other (OTH)

AF:

0.276

AC:

583

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1526

3051

4577

6102

7628

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

408

816

1224

1632

2040

<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:

0.153

Hom.:

284

Bravo

AF:

0.268

Asia WGS

AF:

0.297

AC:

1032

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

5.5

(source)

DANN

Benign

0.75

PhyloP100

0.098

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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