chr12-112911881-T-C

Position:

• chr12-112911881-T-C

Variant summary

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

The NM_016816.4(OAS1):​c.654+646T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0878 in 152,252 control chromosomes in the GnomAD database, including 1,951 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 0.088 (1951 hom., cov: 32)
• Consequence: OAS1 NM_016816.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.219

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OAS1	NM_016816.4	c.654+646T>C		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+646T>C		intron_variant		1	NM_016816.4	ENSP00000202917	P2
	ENST00000552784.1	n.354-3203A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0878 AC: 13358 AN: 152134 Hom.: 1947 Cov.: 32

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0375

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00153

Gnomad OTH AF: 0.0636

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

GnomAD4 genome AF: 0.0878 AC: 13371 AN: 152252 Hom.: 1951 Cov.: 32 AF XY: 0.0851 AC XY: 6337 AN XY: 74470

Gnomad4 AFR AF: 0.302

Gnomad4 AMR AF: 0.0374

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00151

Gnomad4 OTH AF: 0.0629

Alfa AF: 0.0477 Hom.: 193

Bravo AF: 0.101

Asia WGS AF: 0.0160 AC: 56 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	11
DANN	Benign	0.75

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: rs12307655; hg19: chr12-113349686;