rs3738579

Variant names:

• chr1-182586901-A-C
• rs3738579
• NM_021133.4:c.-95T>G

Your query was ambiguous. Multiple possible variants found:

• chr1-182586901-A-C
• chr1-182586901-A-G
• chr1-182586901-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021133.4(RNASEL):​c.-95T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000072 in 1,389,270 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: RNASEL NM_021133.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.569
• Publications: 0 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNASEL	NM_021133.4	c.-95T>G		5_prime_UTR_variant	Exon 2 of 7	ENST00000367559.7	NP_066956.1
RNASEL	XM_047427096.1	c.-95T>G		5_prime_UTR_variant	Exon 2 of 7		XP_047283052.1
RNASEL	XM_047427106.1	c.-95T>G		5_prime_UTR_variant	Exon 2 of 6		XP_047283062.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNASEL	ENST00000367559.7	c.-95T>G		5_prime_UTR_variant	Exon 2 of 7	1	NM_021133.4	ENSP00000356530.3
RNASEL	ENST00000539397.1	c.-95T>G		5_prime_UTR_variant	Exon 2 of 6	2		ENSP00000440844.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.20e-7 AC: 1 AN: 1389270 Hom.: 0 Cov.: 22 AF XY: 0.00000144 AC XY: 1 AN XY: 695114

African (AFR) AF: 0.00 AC: 0 AN: 32004

American (AMR) AF: 0.00 AC: 0 AN: 44524

Ashkenazi Jewish (ASJ) AF: 0.0000389 AC: 1 AN: 25726

East Asian (EAS) AF: 0.00 AC: 0 AN: 39374

South Asian (SAS) AF: 0.00 AC: 0 AN: 84310

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47286

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4060

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1053968

Other (OTH) AF: 0.00 AC: 0 AN: 58018

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.3
DANN	Benign	0.78
PhyloP100		0.57

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

Other links and lift over

dbSNP: rs3738579; hg19: chr1-182556036;