1-182586901-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021133.4(RNASEL):​c.-95T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 1,539,808 control chromosomes in the GnomAD database, including 86,593 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 0.28 (6670 hom., cov: 33)
  • Exomes 𝑓: 0.33 (79923 hom.)
• Consequence: RNASEL NM_021133.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.569
• Publications: 24 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.357 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNASEL	NM_021133.4	MANE Select	c.-95T>C		5_prime_UTR	Exon 2 of 7	NP_066956.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNASEL	ENST00000367559.7	TSL:1 MANE Select	c.-95T>C		5_prime_UTR	Exon 2 of 7	ENSP00000356530.3
	RNASEL	ENST00000539397.1	TSL:2	c.-95T>C		5_prime_UTR	Exon 2 of 6	ENSP00000440844.1

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41949 AN: 152088 Hom.: 6673 Cov.: 33

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.361

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.291

GnomAD4 exome AF: 0.333 AC: 462718 AN: 1387602 Hom.: 79923 Cov.: 22 AF XY: 0.333 AC XY: 231443 AN XY: 694340

African (AFR) AF: 0.111 AC: 3543 AN: 31984

American (AMR) AF: 0.173 AC: 7707 AN: 44516

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 7723 AN: 25718

East Asian (EAS) AF: 0.221 AC: 8715 AN: 39368

South Asian (SAS) AF: 0.293 AC: 24683 AN: 84276

European-Finnish (FIN) AF: 0.373 AC: 17633 AN: 47252

Middle Eastern (MID) AF: 0.291 AC: 1180 AN: 4060

European-Non Finnish (NFE) AF: 0.355 AC: 373318 AN: 1052490

Other (OTH) AF: 0.314 AC: 18216 AN: 57938

GnomAD4 genome AF: 0.276 AC: 41950 AN: 152206 Hom.: 6670 Cov.: 33 AF XY: 0.276 AC XY: 20513 AN XY: 74410

African (AFR) AF: 0.121 AC: 5023 AN: 41548

American (AMR) AF: 0.245 AC: 3744 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 993 AN: 3472

East Asian (EAS) AF: 0.240 AC: 1242 AN: 5182

South Asian (SAS) AF: 0.291 AC: 1407 AN: 4828

European-Finnish (FIN) AF: 0.378 AC: 3988 AN: 10556

Middle Eastern (MID) AF: 0.298 AC: 87 AN: 292

European-Non Finnish (NFE) AF: 0.361 AC: 24519 AN: 68010

Other (OTH) AF: 0.293 AC: 618 AN: 2110

Alfa AF: 0.328 Hom.: 34522

Bravo AF: 0.256

Asia WGS AF: 0.288 AC: 1004 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.7
DANN	Benign	0.77
PhyloP100		0.57
Mutation Taster		=300/0	polymorphism (auto)

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;