12-121033534-G-A

Variant names:

• chr12-121033534-G-A
• rs3213545
• NM_003733.4:c.408C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_003733.4(OASL):​c.408C>T​(p.Leu136Leu) 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
• Publications: 64 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003733.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OASL	NM_003733.4	MANE Select	c.408C>T	p.Leu136Leu	synonymous	Exon 2 of 6	NP_003724.1
	OASL	NM_001261825.2		c.408C>T	p.Leu136Leu	synonymous	Exon 2 of 4	NP_001248754.1
	OASL	NM_001395419.1		c.408C>T	p.Leu136Leu	synonymous	Exon 2 of 6	NP_001382348.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OASL	ENST00000257570.10	TSL:1 MANE Select	c.408C>T	p.Leu136Leu	synonymous	Exon 2 of 6	ENSP00000257570.4
	OASL	ENST00000620239.6	TSL:1	c.408C>T	p.Leu136Leu	synonymous	Exon 2 of 4	ENSP00000479512.1
	OASL	ENST00000339275.10	TSL:1	c.408C>T	p.Leu136Leu	synonymous	Exon 2 of 5	ENSP00000341125.5

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

GnomAD2 exomes AF: 0.316 AC: 79298 AN: 250948 AF XY: 0.325

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 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

African (AFR) AF: 0.146 AC: 4873 AN: 33480

American (AMR) AF: 0.257 AC: 11486 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.435 AC: 11371 AN: 26136

East Asian (EAS) AF: 0.504 AC: 20016 AN: 39700

South Asian (SAS) AF: 0.417 AC: 35928 AN: 86256

European-Finnish (FIN) AF: 0.300 AC: 16012 AN: 53418

Middle Eastern (MID) AF: 0.450 AC: 2597 AN: 5768

European-Non Finnish (NFE) AF: 0.285 AC: 316609 AN: 1111958

Other (OTH) AF: 0.312 AC: 18813 AN: 60390

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

African (AFR) AF: 0.148 AC: 6159 AN: 41486

American (AMR) AF: 0.270 AC: 4123 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.430 AC: 1491 AN: 3470

East Asian (EAS) AF: 0.476 AC: 2440 AN: 5128

South Asian (SAS) AF: 0.413 AC: 1991 AN: 4824

European-Finnish (FIN) AF: 0.312 AC: 3302 AN: 10578

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.289 AC: 19666 AN: 67942

Other (OTH) AF: 0.293 AC: 617 AN: 2108

Alfa AF: 0.278 Hom.: 18275

Bravo AF: 0.253

Asia WGS AF: 0.424 AC: 1471 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.32
DANN	Benign	0.41
PhyloP100		-0.55
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: rs3213545; hg19: chr12-121471337; COSMIC: COSV57477509;