1-182580594-T-C

Position:

• chr1-182580594-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021133.4(RNASEL):​c.1905+631A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0419 in 152,320 control chromosomes in the GnomAD database, including 217 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 0.042 (217 hom., cov: 33)
• Consequence: RNASEL NM_021133.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.106

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0901 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNASEL	NM_021133.4	c.1905+631A>G		intron_variant		ENST00000367559.7	NP_066956.1
RNASEL	XM_047427096.1	c.1906-587A>G		intron_variant			XP_047283052.1
RNASEL	XM_047427106.1	c.1906-587A>G		intron_variant			XP_047283062.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNASEL	ENST00000367559.7	c.1905+631A>G		intron_variant		1	NM_021133.4	ENSP00000356530	P1
RNASEL	ENST00000539397.1	c.1906-587A>G		intron_variant		2		ENSP00000440844

Frequencies

GnomAD3 genomes AF: 0.0419 AC: 6383 AN: 152202 Hom.: 217 Cov.: 33

Gnomad AFR AF: 0.0927

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0231

Gnomad ASJ AF: 0.00893

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00725

Gnomad FIN AF: 0.0118

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0278

Gnomad OTH AF: 0.0330

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

GnomAD4 genome AF: 0.0419 AC: 6383 AN: 152320 Hom.: 217 Cov.: 33 AF XY: 0.0402 AC XY: 2993 AN XY: 74488

Gnomad4 AFR AF: 0.0925

Gnomad4 AMR AF: 0.0231

Gnomad4 ASJ AF: 0.00893

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00684

Gnomad4 FIN AF: 0.0118

Gnomad4 NFE AF: 0.0279

Gnomad4 OTH AF: 0.0326

Alfa AF: 0.0357 Hom.: 33

Bravo AF: 0.0462

Asia WGS AF: 0.00837 AC: 30 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	2.9
DANN	Benign	0.66

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

Publications

LitVar

Other links and lift over

dbSNP: rs12736689; hg19: chr1-182549729;