12-121034128-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.199-385G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 151,528 control chromosomes in the GnomAD database, including 1,690 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 (1690 hom., cov: 31)
• Consequence: OASL NM_003733.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44

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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OASL	NM_003733.4	c.199-385G>A		intron_variant		ENST00000257570.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OASL	ENST00000257570.10	c.199-385G>A		intron_variant		1	NM_003733.4	P1

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20522 AN: 151430 Hom.: 1689 Cov.: 31

Gnomad AFR AF: 0.0604

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.00194

Gnomad SAS AF: 0.0371

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.172

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.154

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

GnomAD4 genome AF: 0.135 AC: 20516 AN: 151528 Hom.: 1690 Cov.: 31 AF XY: 0.132 AC XY: 9748 AN XY: 73944

Gnomad4 AFR AF: 0.0602

Gnomad4 AMR AF: 0.115

Gnomad4 ASJ AF: 0.196

Gnomad4 EAS AF: 0.00194

Gnomad4 SAS AF: 0.0373

Gnomad4 FIN AF: 0.224

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.152

Alfa AF: 0.162 Hom.: 1616

Bravo AF: 0.127

Asia WGS AF: 0.0340 AC: 121 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.61
Dann	Benign	0.27

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: rs7965349; hg19: chr12-121471931;