rs2240189

Positions:

• chr12-112965692-G-A

Variant summary

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

The NM_006187.4(OAS3):​c.2404-52G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 1,541,466 control chromosomes in the GnomAD database, including 53,531 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 0.24 (4486 hom., cov: 33)
  • Exomes 𝑓: 0.26 (49045 hom.)
• Consequence: OAS3 NM_006187.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.341

Genes affected

OAS3 (HGNC:8088): (2'-5'-oligoadenylate synthetase 3) This gene encodes an enzyme included in the 2', 5' oligoadenylate synthase family. This enzyme is induced by interferons and catalyzes the 2', 5' oligomers of adenosine in order to bind and activate RNase L. This enzyme family plays a significant role in the inhibition of cellular protein synthesis and viral infection resistance. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OAS3	NM_006187.4	c.2404-52G>A		intron_variant		ENST00000228928.12
OAS3	NM_001410984.1	c.2404-205G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OAS3	ENST00000228928.12	c.2404-52G>A		intron_variant		1	NM_006187.4	P3
	ENST00000552784.1	n.353+51707C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35784 AN: 152062 Hom.: 4487 Cov.: 33

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.217

GnomAD4 exome AF: 0.262 AC: 364551 AN: 1389286 Hom.: 49045 AF XY: 0.260 AC XY: 177949 AN XY: 685094

Gnomad4 AFR exome AF: 0.152

Gnomad4 AMR exome AF: 0.316

Gnomad4 ASJ exome AF: 0.201

Gnomad4 EAS exome AF: 0.172

Gnomad4 SAS exome AF: 0.196

Gnomad4 FIN exome AF: 0.259

Gnomad4 NFE exome AF: 0.275

Gnomad4 OTH exome AF: 0.243

GnomAD4 genome AF: 0.235 AC: 35799 AN: 152180 Hom.: 4486 Cov.: 33 AF XY: 0.235 AC XY: 17504 AN XY: 74410

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.306

Gnomad4 ASJ AF: 0.208

Gnomad4 EAS AF: 0.156

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.264

Gnomad4 NFE AF: 0.269

Gnomad4 OTH AF: 0.214

Alfa AF: 0.248 Hom.: 1024

Bravo AF: 0.239

Asia WGS AF: 0.196 AC: 683 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	4.0
DANN	Benign	0.66

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: rs2240189; hg19: chr12-113403497; COSMIC: COSV57448496; COSMIC: COSV57448496;