rs36053738

Variant names:

• chr1-182575446-C-T
• rs36053738
• NM_021133.4:c.2172G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_021133.4(RNASEL):​c.2172G>A​(p.Lys724Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0392 in 1,614,144 control chromosomes in the GnomAD database, including 1,615 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.030 (113 hom., cov: 31)
  • Exomes 𝑓: 0.040 (1502 hom.)
• Consequence: RNASEL NM_021133.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.129
• Publications: 10 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 1-182575446-C-T is Benign according to our data. Variant chr1-182575446-C-T is described in ClinVar as Benign. ClinVar VariationId is 3055991.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0295 (4498/152266) while in subpopulation NFE AF = 0.046 (3130/68014). AF 95% confidence interval is 0.0447. There are 113 homozygotes in GnomAd4. There are 2222 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 4498 AD gene.

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.2172G>A	p.Lys724Lys	synonymous	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.2172G>A	p.Lys724Lys	synonymous	Exon 7 of 7	ENSP00000356530.3	Q05823-1
	RNASEL	ENST00000946546.1		c.2172G>A	p.Lys724Lys	synonymous	Exon 7 of 7	ENSP00000616605.1
	RNASEL	ENST00000890859.1		c.2163G>A	p.Lys721Lys	synonymous	Exon 7 of 7	ENSP00000560918.1

Frequencies

GnomAD3 genomes AF: 0.0296 AC: 4497 AN: 152148 Hom.: 113 Cov.: 31

Gnomad AFR AF: 0.00813

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.00806

Gnomad ASJ AF: 0.00980

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00765

Gnomad FIN AF: 0.0727

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0460

Gnomad OTH AF: 0.0153

GnomAD2 exomes AF: 0.0308 AC: 7752 AN: 251402 AF XY: 0.0304

Gnomad AFR exome AF: 0.00652

Gnomad AMR exome AF: 0.00726

Gnomad ASJ exome AF: 0.0118

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0741

Gnomad NFE exome AF: 0.0464

Gnomad OTH exome AF: 0.0251

GnomAD4 exome AF: 0.0402 AC: 58817 AN: 1461878 Hom.: 1502 Cov.: 31 AF XY: 0.0389 AC XY: 28316 AN XY: 727244

African (AFR) AF: 0.00618 AC: 207 AN: 33480

American (AMR) AF: 0.00803 AC: 359 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0127 AC: 331 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00876 AC: 756 AN: 86258

European-Finnish (FIN) AF: 0.0720 AC: 3848 AN: 53414

Middle Eastern (MID) AF: 0.00451 AC: 26 AN: 5768

European-Non Finnish (NFE) AF: 0.0462 AC: 51412 AN: 1112002

Other (OTH) AF: 0.0311 AC: 1877 AN: 60396

GnomAD4 genome AF: 0.0295 AC: 4498 AN: 152266 Hom.: 113 Cov.: 31 AF XY: 0.0298 AC XY: 2222 AN XY: 74446

African (AFR) AF: 0.00811 AC: 337 AN: 41564

American (AMR) AF: 0.00804 AC: 123 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00980 AC: 34 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5192

South Asian (SAS) AF: 0.00787 AC: 38 AN: 4830

European-Finnish (FIN) AF: 0.0727 AC: 770 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0460 AC: 3130 AN: 68014

Other (OTH) AF: 0.0152 AC: 32 AN: 2112

Alfa AF: 0.0393 Hom.: 104

Bravo AF: 0.0241

Asia WGS AF: 0.00491 AC: 18 AN: 3478

EpiCase AF: 0.0380

EpiControl AF: 0.0370

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	RNASEL-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	5.3
DANN	Benign	0.56
PhyloP100		0.13
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: rs36053738; hg19: chr1-182544581;