rs12818640

Positions:

• chr12-112974066-T-C
• chr12-112974066-T-G

Variant summary

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

The ENST00000552784.1(ENSG00000257452):​n.353+43333A>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,186 control chromosomes in the GnomAD database, including 2,408 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 0.17 (2408 hom., cov: 32)
• Consequence: ENST00000552784.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.446

Genes affected

(HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000552784.1	n.353+43333A>G		intron_variant, non_coding_transcript_variant		4
OAS3	ENST00000681497.1	c.*4093T>C		3_prime_UTR_variant	16/16			ENSP00000505225

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26158 AN: 152068 Hom.: 2411 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.182

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.172 AC: 26164 AN: 152186 Hom.: 2408 Cov.: 32 AF XY: 0.175 AC XY: 12989 AN XY: 74396

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.190

Gnomad4 ASJ AF: 0.191

Gnomad4 EAS AF: 0.325

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.205

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.180

Alfa AF: 0.172 Hom.: 274

Bravo AF: 0.170

Asia WGS AF: 0.204 AC: 709 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.4
DANN	Benign	0.56

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12818640; hg19: chr12-113411871;