rs2072136

Positions:

• chr12-112961114-G-A
• chr12-112961114-G-C

Variant summary

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

The NM_006187.4(OAS3):​c.1701G>A​(p.Ser567=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 1,612,810 control chromosomes in the GnomAD database, including 58,973 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 0.23 (5145 hom., cov: 33)
  • Exomes 𝑓: 0.26 (53828 hom.)
• Consequence: OAS3 NM_006187.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP7: Synonymous conserved (PhyloP=-1.11 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OAS3	NM_006187.4	c.1701G>A	p.Ser567=	synonymous_variant	8/16	ENST00000228928.12
OAS3	NM_001410984.1	c.1701G>A	p.Ser567=	synonymous_variant	8/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OAS3	ENST00000228928.12	c.1701G>A	p.Ser567=	synonymous_variant	8/16	1	NM_006187.4	P3
	ENST00000552784.1	n.354-52436C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35348 AN: 151598 Hom.: 5138 Cov.: 33

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.656

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.234

GnomAD3 exomes AF: 0.307 AC: 76067 AN: 248092 Hom.: 13995 AF XY: 0.304 AC XY: 40976 AN XY: 134582

Gnomad AFR exome AF: 0.106

Gnomad AMR exome AF: 0.387

Gnomad ASJ exome AF: 0.155

Gnomad EAS exome AF: 0.669

Gnomad SAS exome AF: 0.372

Gnomad FIN exome AF: 0.375

Gnomad NFE exome AF: 0.237

Gnomad OTH exome AF: 0.261

GnomAD4 exome AF: 0.256 AC: 373939 AN: 1461094 Hom.: 53828 Cov.: 35 AF XY: 0.259 AC XY: 188293 AN XY: 726790

Gnomad4 AFR exome AF: 0.0973

Gnomad4 AMR exome AF: 0.369

Gnomad4 ASJ exome AF: 0.157

Gnomad4 EAS exome AF: 0.648

Gnomad4 SAS exome AF: 0.372

Gnomad4 FIN exome AF: 0.373

Gnomad4 NFE exome AF: 0.231

Gnomad4 OTH exome AF: 0.247

GnomAD4 genome AF: 0.233 AC: 35367 AN: 151716 Hom.: 5145 Cov.: 33 AF XY: 0.245 AC XY: 18141 AN XY: 74150

Gnomad4 AFR AF: 0.110

Gnomad4 AMR AF: 0.276

Gnomad4 ASJ AF: 0.142

Gnomad4 EAS AF: 0.657

Gnomad4 SAS AF: 0.383

Gnomad4 FIN AF: 0.372

Gnomad4 NFE AF: 0.240

Gnomad4 OTH AF: 0.234

Alfa AF: 0.227 Hom.: 5529

Bravo AF: 0.218

Asia WGS AF: 0.428 AC: 1485 AN: 3478

EpiCase AF: 0.219

EpiControl AF: 0.210

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.1
DANN	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2072136; hg19: chr12-113398919; COSMIC: COSV57449812; COSMIC: COSV57449812;