12-112912991-G-T

Variant summary

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

The NM_016816.4(OAS1):c.654+1756G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.753 in 152,166 control chromosomes in the GnomAD database, including 44,319 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 0.75 (44319 hom., cov: 32)
• Consequence: OAS1 NM_016816.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.192

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.93 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OAS1	NM_016816.4	c.654+1756G>T		intron_variant		ENST00000202917.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OAS1	ENST00000202917.10	c.654+1756G>T		intron_variant		1	NM_016816.4	P2
	ENST00000552784.1	n.354-4313C>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.752 AC: 114375 AN: 152048 Hom.: 44250 Cov.: 32

Gnomad AFR AF: 0.938

Gnomad AMI AF: 0.684

Gnomad AMR AF: 0.767

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.774

Gnomad SAS AF: 0.708

Gnomad FIN AF: 0.729

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.657

Gnomad OTH AF: 0.704

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

GnomAD4 genome AF: 0.753 AC: 114509 AN: 152166 Hom.: 44319 Cov.: 32 AF XY: 0.755 AC XY: 56145 AN XY: 74388

Gnomad4 AFR AF: 0.938

Gnomad4 AMR AF: 0.767

Gnomad4 ASJ AF: 0.501

Gnomad4 EAS AF: 0.775

Gnomad4 SAS AF: 0.708

Gnomad4 FIN AF: 0.729

Gnomad4 NFE AF: 0.657

Gnomad4 OTH AF: 0.707

Alfa AF: 0.728 Hom.: 6486

Bravo AF: 0.765

Asia WGS AF: 0.768 AC: 2670 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.98
Dann	Benign	0.42

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: rs2057778; hg19: chr12-113350796;