rs3803057

Positions:

• chr12-112930929-G-A

Variant summary

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

The ENST00000552784.1(ENSG00000257452):​n.354-22251C>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0652 in 152,168 control chromosomes in the GnomAD database, including 541 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 0.065 (541 hom., cov: 33)
• Consequence: ENST00000552784.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.259

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OAS1	NM_001320151.2	c.1039-949G>A		intron_variant			NP_001307080.1
OAS1	NM_001406025.1	c.1015-949G>A		intron_variant			NP_001392954.1
OAS1	NR_175991.1	n.1344-949G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OAS1	ENST00000540589.3	c.1168-949G>A		intron_variant		1		ENSP00000474083
OAS1	ENST00000551241.6	c.1039-949G>A		intron_variant		1		ENSP00000448790
OAS1	ENST00000552526.2	c.1083-949G>A		intron_variant		1		ENSP00000475139	A2
	ENST00000552784.1	n.354-22251C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0651 AC: 9906 AN: 152050 Hom.: 541 Cov.: 33

Gnomad AFR AF: 0.0326

Gnomad AMI AF: 0.0593

Gnomad AMR AF: 0.0917

Gnomad ASJ AF: 0.0590

Gnomad EAS AF: 0.312

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0498

Gnomad OTH AF: 0.0646

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

GnomAD4 genome AF: 0.0652 AC: 9915 AN: 152168 Hom.: 541 Cov.: 33 AF XY: 0.0714 AC XY: 5309 AN XY: 74384

Gnomad4 AFR AF: 0.0325

Gnomad4 AMR AF: 0.0923

Gnomad4 ASJ AF: 0.0590

Gnomad4 EAS AF: 0.313

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.0499

Gnomad4 OTH AF: 0.0644

Alfa AF: 0.0541 Hom.: 394

Bravo AF: 0.0647

Asia WGS AF: 0.148 AC: 515 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.0
DANN	Benign	0.33

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3803057; hg19: chr12-113368734;