Genetic Variant 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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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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
RNASEL	NM_021133.4 link	c.-379T>C	upstream_gene_variant	ENST00000367559.7	NP_066956.1	Q05823-1
RNASEL	XM_047427096.1 link	c.-379T>C	upstream_gene_variant		XP_047283052.1
RNASEL	XM_047427106.1 link	c.-379T>C	upstream_gene_variant		XP_047283062.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNASEL	ENST00000367559.7 link	c.-379T>C		upstream_gene_variant		1	NM_021133.4	ENSP00000356530.3		Q05823-1
RNASEL	ENST00000539397.1 link	c.-379T>C		upstream_gene_variant		2		ENSP00000440844.1		Q05823-2

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 v4.3

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over