1-182573716-G-C

Variant names:

• chr1-182573716-G-C
• rs1048260
• NM_021133.4:c.*1676C>G

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0980
• Publications: 12 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=-0.86).
• 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	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.: 33

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.: 0 AF XY: 0.270 AC XY: 3788 AN XY: 14010

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: 99 AN: 266

European-Finnish (FIN) AF: 0.357 AC: 5 AN: 14

Middle Eastern (MID) AF: 0.354 AC: 68 AN: 192

European-Non Finnish (NFE) AF: 0.284 AC: 5040 AN: 17776

Other (OTH) AF: 0.284 AC: 692 AN: 2440

GnomAD4 genome AF: 0.262 AC: 39794 AN: 152158 Hom.: 5633 Cov.: 33 AF XY: 0.262 AC XY: 19474 AN XY: 74400

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

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
DANN	Benign	0.75
PhyloP100		0.098
Mutation Taster		=100/0	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: rs1048260; hg19: chr1-182542851;