rs12811390

Positions:

• chr12-121032217-C-T

Variant summary

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

The NM_003733.4(OASL):​c.482-600G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 151,930 control chromosomes in the GnomAD database, including 1,859 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 0.14 (1859 hom., cov: 31)
• Consequence: OASL NM_003733.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.559

Genes affected

OASL (HGNC:8090): (2'-5'-oligoadenylate synthetase like) Enables DNA binding activity and double-stranded RNA binding activity. Involved in several processes, including interleukin-27-mediated signaling pathway; negative regulation of viral genome replication; and positive regulation of RIG-I signaling pathway. Located in cytosol; nucleolus; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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 (NFE) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OASL	NM_003733.4	c.482-600G>A		intron_variant		ENST00000257570.10	NP_003724.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OASL	ENST00000257570.10	c.482-600G>A		intron_variant		1	NM_003733.4	ENSP00000257570	P1

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21885 AN: 151812 Hom.: 1858 Cov.: 31

Gnomad AFR AF: 0.0695

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.121

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

GnomAD4 genome AF: 0.144 AC: 21894 AN: 151930 Hom.: 1859 Cov.: 31 AF XY: 0.146 AC XY: 10854 AN XY: 74260

Gnomad4 AFR AF: 0.0694

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.204

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.120

Alfa AF: 0.177 Hom.: 354

Bravo AF: 0.130

Asia WGS AF: 0.0960 AC: 331 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	1.4
DANN	Benign	0.84

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: rs12811390; hg19: chr12-121470020;