12-121034128-C-T

Variant names:

• chr12-121034128-C-T
• rs7965349
• NM_003733.4:c.199-385G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 20 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
OASL	NM_003733.4	c.199-385G>A		intron_variant	Intron 1 of 5	ENST00000257570.10	NP_003724.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OASL	ENST00000257570.10	c.199-385G>A		intron_variant	Intron 1 of 5	1	NM_003733.4	ENSP00000257570.4

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

African (AFR) AF: 0.0602 AC: 2491 AN: 41348

American (AMR) AF: 0.115 AC: 1747 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 679 AN: 3472

East Asian (EAS) AF: 0.00194 AC: 10 AN: 5146

South Asian (SAS) AF: 0.0373 AC: 179 AN: 4796

European-Finnish (FIN) AF: 0.224 AC: 2318 AN: 10360

Middle Eastern (MID) AF: 0.164 AC: 48 AN: 292

European-Non Finnish (NFE) AF: 0.186 AC: 12659 AN: 67884

Other (OTH) AF: 0.152 AC: 318 AN: 2098

Alfa AF: 0.163 Hom.: 1907

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
PhyloP100		-1.4
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: rs7965349; hg19: chr12-121471931;