1-182580201-A-G

Variant names:

• chr1-182580201-A-G
• rs579006
• NM_021133.4:c.1905+1024T>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.1905+1024T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 152,120 control chromosomes in the GnomAD database, including 8,627 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 0.33 (8627 hom., cov: 33)
• Consequence: RNASEL NM_021133.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0580
• Publications: 11 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNASEL	NM_021133.4	c.1905+1024T>C		intron_variant	Intron 5 of 6	ENST00000367559.7	NP_066956.1
RNASEL	XM_047427096.1	c.1906-194T>C		intron_variant	Intron 5 of 6		XP_047283052.1
RNASEL	XM_047427106.1	c.1906-194T>C		intron_variant	Intron 5 of 5		XP_047283062.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNASEL	ENST00000367559.7	c.1905+1024T>C		intron_variant	Intron 5 of 6	1	NM_021133.4	ENSP00000356530.3
RNASEL	ENST00000539397.1	c.1906-194T>C		intron_variant	Intron 5 of 5	2		ENSP00000440844.1

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50752 AN: 152002 Hom.: 8625 Cov.: 33

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.335

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.334 AC: 50779 AN: 152120 Hom.: 8627 Cov.: 33 AF XY: 0.332 AC XY: 24692 AN XY: 74366

African (AFR) AF: 0.303 AC: 12587 AN: 41488

American (AMR) AF: 0.274 AC: 4190 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1084 AN: 3468

East Asian (EAS) AF: 0.242 AC: 1255 AN: 5188

South Asian (SAS) AF: 0.278 AC: 1342 AN: 4824

European-Finnish (FIN) AF: 0.377 AC: 3985 AN: 10576

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.371 AC: 25243 AN: 67974

Other (OTH) AF: 0.336 AC: 710 AN: 2114

Alfa AF: 0.343 Hom.: 13601

Bravo AF: 0.321

Asia WGS AF: 0.294 AC: 1026 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.45
DANN	Benign	0.54
PhyloP100		0.058
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: rs579006; hg19: chr1-182549336;