chr12-112961374-C-T

Position:

• chr12-112961374-C-T

Variant summary

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

The ENST00000228928.12(OAS3):​c.1833+128C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 816,368 control chromosomes in the GnomAD database, including 25,750 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 (4202 hom., cov: 32)
  • Exomes 𝑓: 0.25 (21548 hom.)
• Consequence: OAS3 ENST00000228928.12 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.181

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OAS3	NM_006187.4	c.1833+128C>T		intron_variant		ENST00000228928.12	NP_006178.2
OAS3	NM_001410984.1	c.1833+128C>T		intron_variant			NP_001397913.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OAS3	ENST00000228928.12	c.1833+128C>T		intron_variant		1	NM_006187.4	ENSP00000228928	P3
	ENST00000552784.1	n.354-52696G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34238 AN: 151980 Hom.: 4204 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.212

GnomAD4 exome AF: 0.248 AC: 164981 AN: 664270 Hom.: 21548 AF XY: 0.246 AC XY: 83224 AN XY: 338650

Gnomad4 AFR exome AF: 0.133

Gnomad4 AMR exome AF: 0.311

Gnomad4 ASJ exome AF: 0.201

Gnomad4 EAS exome AF: 0.172

Gnomad4 SAS exome AF: 0.197

Gnomad4 FIN exome AF: 0.241

Gnomad4 NFE exome AF: 0.264

Gnomad4 OTH exome AF: 0.237

GnomAD4 genome AF: 0.225 AC: 34253 AN: 152098 Hom.: 4202 Cov.: 32 AF XY: 0.225 AC XY: 16734 AN XY: 74364

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.304

Gnomad4 ASJ AF: 0.206

Gnomad4 EAS AF: 0.157

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.241

Gnomad4 NFE AF: 0.265

Gnomad4 OTH AF: 0.209

Alfa AF: 0.257 Hom.: 6827

Bravo AF: 0.229

Asia WGS AF: 0.197 AC: 688 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.3
DANN	Benign	0.63

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: rs2072135; hg19: chr12-113399179;