12-112952874-T-C

Variant names:

• chr12-112952874-T-C
• rs7970893
• NM_006187.4:c.1657+1899T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000228928.12(OAS3):​c.1657+1899T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 152,020 control chromosomes in the GnomAD database, including 26,971 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 0.59 (26971 hom., cov: 32)
• Consequence: OAS3 ENST00000228928.12 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.453
• Publications: 20 publications found

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]

ENSG00000257452 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000228928.12. 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
	OAS3	NM_006187.4	MANE Select	c.1657+1899T>C		intron	N/A	NP_006178.2
	OAS3	NM_001410984.1		c.1657+1899T>C		intron	N/A	NP_001397913.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OAS3	ENST00000228928.12	TSL:1 MANE Select	c.1657+1899T>C		intron	N/A	ENSP00000228928.7
	OAS3	ENST00000679493.1		c.1657+1899T>C		intron	N/A	ENSP00000506397.1
	OAS3	ENST00000681346.1		c.1657+1899T>C		intron	N/A	ENSP00000505939.1

Frequencies

GnomAD3 genomes AF: 0.588 AC: 89390 AN: 151902 Hom.: 26934 Cov.: 32

Gnomad AFR AF: 0.608

Gnomad AMI AF: 0.537

Gnomad AMR AF: 0.645

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.902

Gnomad SAS AF: 0.661

Gnomad FIN AF: 0.669

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.534

Gnomad OTH AF: 0.540

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

GnomAD4 genome AF: 0.589 AC: 89488 AN: 152020 Hom.: 26971 Cov.: 32 AF XY: 0.599 AC XY: 44485 AN XY: 74310

African (AFR) AF: 0.608 AC: 25221 AN: 41456

American (AMR) AF: 0.645 AC: 9864 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 1417 AN: 3466

East Asian (EAS) AF: 0.902 AC: 4663 AN: 5172

South Asian (SAS) AF: 0.662 AC: 3189 AN: 4816

European-Finnish (FIN) AF: 0.669 AC: 7055 AN: 10550

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.534 AC: 36324 AN: 67962

Other (OTH) AF: 0.545 AC: 1150 AN: 2110

Alfa AF: 0.547 Hom.: 96324

Bravo AF: 0.589

Asia WGS AF: 0.767 AC: 2667 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.8
DANN	Benign	0.45
PhyloP100		-0.45
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: rs7970893; hg19: chr12-113390679;