12-112929504-C-T

Position:

• chr12-112929504-C-T

Variant summary

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

The ENST00000540589.3(OAS1):​c.1168-2374C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.744 in 152,164 control chromosomes in the GnomAD database, including 43,390 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 0.74 (43390 hom., cov: 32)
• Consequence: OAS1 ENST00000540589.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.792

Genes affected

OAS1 (HGNC:8086): (2'-5'-oligoadenylate synthetase 1) This interferon-induced gene encodes a protein that synthesizes 2',5'-oligoadenylates (2-5As). This protein plays a key role in innate cellular antiviral response, and has been implicated in other cellular processes like cell growth and apoptosis. Alternative splicing results in multiple transcript variants with different enzymatic activities. Polymorphisms in this gene have been associated with susceptibility to viral infection, including SARS-CoV-2, and diabetes mellitus, type 1. This gene is located in a cluster of related genes on chromosome 12. [provided by RefSeq, May 2022]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.928 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OAS1	NM_001320151.2	c.1039-2374C>T		intron_variant			NP_001307080.1
OAS1	NM_001406025.1	c.1015-2374C>T		intron_variant			NP_001392954.1
OAS1	NR_175991.1	n.1344-2374C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OAS1	ENST00000540589.3	c.1168-2374C>T		intron_variant		1		ENSP00000474083
OAS1	ENST00000551241.6	c.1039-2374C>T		intron_variant		1		ENSP00000448790
OAS1	ENST00000552526.2	c.1083-2374C>T		intron_variant		1		ENSP00000475139	A2
	ENST00000552784.1	n.354-20826G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.744 AC: 113053 AN: 152046 Hom.: 43326 Cov.: 32

Gnomad AFR AF: 0.935

Gnomad AMI AF: 0.617

Gnomad AMR AF: 0.752

Gnomad ASJ AF: 0.499

Gnomad EAS AF: 0.775

Gnomad SAS AF: 0.709

Gnomad FIN AF: 0.727

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.644

Gnomad OTH AF: 0.691

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

GnomAD4 genome AF: 0.744 AC: 113181 AN: 152164 Hom.: 43390 Cov.: 32 AF XY: 0.747 AC XY: 55531 AN XY: 74372

Gnomad4 AFR AF: 0.935

Gnomad4 AMR AF: 0.752

Gnomad4 ASJ AF: 0.499

Gnomad4 EAS AF: 0.775

Gnomad4 SAS AF: 0.708

Gnomad4 FIN AF: 0.727

Gnomad4 NFE AF: 0.644

Gnomad4 OTH AF: 0.694

Alfa AF: 0.710 Hom.: 5875

Bravo AF: 0.755

Asia WGS AF: 0.769 AC: 2675 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.6
DANN	Benign	0.23

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1859336; hg19: chr12-113367309;