12-112913715-T-G

Position:

• chr12-112913715-T-G

Variant summary

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

The NM_016816.4(OAS1):​c.654+2480T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 151,980 control chromosomes in the GnomAD database, including 30,948 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 0.63 (30948 hom., cov: 32)
• Consequence: OAS1 NM_016816.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0800

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OAS1	NM_016816.4	c.654+2480T>G		intron_variant		ENST00000202917.10	NP_058132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OAS1	ENST00000202917.10	c.654+2480T>G		intron_variant		1	NM_016816.4	ENSP00000202917	P2
	ENST00000552784.1	n.354-5037A>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.632 AC: 95916 AN: 151862 Hom.: 30913 Cov.: 32

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.684

Gnomad AMR AF: 0.716

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.776

Gnomad SAS AF: 0.707

Gnomad FIN AF: 0.728

Gnomad MID AF: 0.564

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.628

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

GnomAD4 genome AF: 0.632 AC: 96012 AN: 151980 Hom.: 30948 Cov.: 32 AF XY: 0.639 AC XY: 47466 AN XY: 74324

Gnomad4 AFR AF: 0.516

Gnomad4 AMR AF: 0.717

Gnomad4 ASJ AF: 0.501

Gnomad4 EAS AF: 0.777

Gnomad4 SAS AF: 0.707

Gnomad4 FIN AF: 0.728

Gnomad4 NFE AF: 0.658

Gnomad4 OTH AF: 0.626

Alfa AF: 0.649 Hom.: 4873

Bravo AF: 0.627

Asia WGS AF: 0.716 AC: 2482 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.5
DANN	Benign	0.72

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: rs2285934; hg19: chr12-113351520;