dbSNP rs2274509: RNASEL:c.-379T>C (chr1-182589381-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.-379T>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 152,050 control chromosomes in the GnomAD database, including 9,943 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 0.36 ( 9942 hom., cov: 32)

Exomes 𝑓: 0.32 ( 1 hom. )

Consequence

RNASEL
NM_021133.4 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.60

Publications

9 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:

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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=-0.83).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.391 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.-379T>C		upstream_gene	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.-379T>C	upstream_gene	N/A	ENSP00000356530.3	Q05823-1
RNASEL	ENST00000946546.1		c.-398T>C	upstream_gene	N/A	ENSP00000616605.1
RNASEL	ENST00000890859.1		c.-379T>C	upstream_gene	N/A	ENSP00000560918.1

Frequencies

GnomAD3 genomes

AF:

0.360

AC:

54642

AN:

151904

Hom.:

9941

Cov.:

show subpopulations

Gnomad AFR

AF:

0.346

Gnomad AMI

AF:

0.405

Gnomad AMR

AF:

0.288

Gnomad ASJ

AF:

0.298

Gnomad EAS

AF:

0.239

Gnomad SAS

AF:

0.299

Gnomad FIN

AF:

0.396

Gnomad MID

AF:

0.322

Gnomad NFE

AF:

0.395

Gnomad OTH

AF:

0.351

GnomAD4 exome

AF:

0.321

AC:

AN:

Hom.:

AF XY:

0.300

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.318

AC:

AN:

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.360

AC:

54661

AN:

152022

Hom.:

9942

Cov.:

AF XY:

0.357

AC XY:

26542

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.346

AC:

14329

AN:

41454

American (AMR)

AF:

0.288

AC:

4398

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.298

AC:

1033

AN:

3470

East Asian (EAS)

AF:

0.239

AC:

1236

AN:

5170

South Asian (SAS)

AF:

0.298

AC:

1436

AN:

4822

European-Finnish (FIN)

AF:

0.396

AC:

4179

AN:

10546

Middle Eastern (MID)

AF:

0.308

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.395

AC:

26848

AN:

67956

Other (OTH)

AF:

0.352

AC:

743

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1796

3591

5387

7182

8978

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

542

1084

1626

2168

2710

<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:

0.372

Hom.:

2781

Bravo

AF:

0.348

Asia WGS

AF:

0.306

AC:

1066

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.2

(source)

DANN

Benign

0.58

PhyloP100

-1.6

PromoterAI

0.015

Neutral

(source)

Splicing

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over