12-112961374-C-T

Variant names:

• chr12-112961374-C-T
• rs2072135
• NM_006187.4:c.1833+128C>T

Variant summary

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

The NM_006187.4(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 NM_006187.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.181
• Publications: 14 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=-0.81).
• 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 rank	MANE	Protein	UniProt
OAS3	NM_006187.4	c.1833+128C>T		intron_variant	Intron 8 of 15	ENST00000228928.12	NP_006178.2
OAS3	NM_001410984.1	c.1833+128C>T		intron_variant	Intron 8 of 15		NP_001397913.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OAS3	ENST00000228928.12	c.1833+128C>T		intron_variant	Intron 8 of 15	1	NM_006187.4	ENSP00000228928.7

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

African (AFR) AF: 0.133 AC: 2192 AN: 16494

American (AMR) AF: 0.311 AC: 5953 AN: 19156

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 3033 AN: 15090

East Asian (EAS) AF: 0.172 AC: 5478 AN: 31904

South Asian (SAS) AF: 0.197 AC: 9748 AN: 49546

European-Finnish (FIN) AF: 0.241 AC: 7551 AN: 31330

Middle Eastern (MID) AF: 0.216 AC: 526 AN: 2434

European-Non Finnish (NFE) AF: 0.264 AC: 122632 AN: 465128

Other (OTH) AF: 0.237 AC: 7868 AN: 33188

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

African (AFR) AF: 0.137 AC: 5698 AN: 41476

American (AMR) AF: 0.304 AC: 4650 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 714 AN: 3470

East Asian (EAS) AF: 0.157 AC: 812 AN: 5176

South Asian (SAS) AF: 0.197 AC: 951 AN: 4822

European-Finnish (FIN) AF: 0.241 AC: 2546 AN: 10576

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.265 AC: 17998 AN: 67968

Other (OTH) AF: 0.209 AC: 443 AN: 2116

Alfa AF: 0.254 Hom.: 8485

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
PhyloP100		-0.18
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: rs2072135; hg19: chr12-113399179;