rs3213545

Positions:

• chr12-121033534-G-A
• chr12-121033534-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_003733.4(OASL):​c.408C>T​(p.Leu136=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 1,613,822 control chromosomes in the GnomAD database, including 73,977 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 0.27 (5856 hom., cov: 31)
  • Exomes 𝑓: 0.30 (68121 hom.)
• Consequence: OASL NM_003733.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.545

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP7: Synonymous conserved (PhyloP=-0.545 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OASL	NM_003733.4	c.408C>T	p.Leu136=	synonymous_variant	2/6	ENST00000257570.10	NP_003724.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OASL	ENST00000257570.10	c.408C>T	p.Leu136=	synonymous_variant	2/6	1	NM_003733.4	ENSP00000257570	P1

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40271 AN: 151880 Hom.: 5854 Cov.: 31

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.430

Gnomad EAS AF: 0.476

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.286

GnomAD3 exomes AF: 0.316 AC: 79298 AN: 250948 Hom.: 13375 AF XY: 0.325 AC XY: 44162 AN XY: 135718

Gnomad AFR exome AF: 0.141

Gnomad AMR exome AF: 0.255

Gnomad ASJ exome AF: 0.431

Gnomad EAS exome AF: 0.478

Gnomad SAS exome AF: 0.420

Gnomad FIN exome AF: 0.302

Gnomad NFE exome AF: 0.297

Gnomad OTH exome AF: 0.318

GnomAD4 exome AF: 0.299 AC: 437705 AN: 1461824 Hom.: 68121 Cov.: 40 AF XY: 0.304 AC XY: 221180 AN XY: 727214

Gnomad4 AFR exome AF: 0.146

Gnomad4 AMR exome AF: 0.257

Gnomad4 ASJ exome AF: 0.435

Gnomad4 EAS exome AF: 0.504

Gnomad4 SAS exome AF: 0.417

Gnomad4 FIN exome AF: 0.300

Gnomad4 NFE exome AF: 0.285

Gnomad4 OTH exome AF: 0.312

GnomAD4 genome AF: 0.265 AC: 40280 AN: 151998 Hom.: 5856 Cov.: 31 AF XY: 0.271 AC XY: 20148 AN XY: 74288

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.270

Gnomad4 ASJ AF: 0.430

Gnomad4 EAS AF: 0.476

Gnomad4 SAS AF: 0.413

Gnomad4 FIN AF: 0.312

Gnomad4 NFE AF: 0.289

Gnomad4 OTH AF: 0.293

Alfa AF: 0.282 Hom.: 8247

Bravo AF: 0.253

Asia WGS AF: 0.424 AC: 1471 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.32
DANN	Benign	0.41

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: rs3213545; hg19: chr12-121471337; COSMIC: COSV57477509;