rs3803057

Variant names:

• chr12-112930929-G-A
• rs3803057
• ENST00000540589.3:c.1168-949G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-112930929-G-A
• chr12-112930929-G-C
• chr12-112930929-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000540589.3(OAS1):​c.1168-949G>A variant causes a intron 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: OAS1 ENST00000540589.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.259
• Publications: 6 publications found

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]

OAS1 Gene-Disease associations (from GenCC):

• pulmonary alveolar proteinosis with hypogammaglobulinemia

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000257452 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
OAS1	NM_001320151.2	c.1039-949G>A		intron_variant	Intron 5 of 5		NP_001307080.1
OAS1	NM_001406025.1	c.1015-949G>A		intron_variant	Intron 5 of 5		NP_001392954.1
OAS1	NR_175991.1	n.1344-949G>A		intron_variant	Intron 6 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OAS1	ENST00000540589.3	c.1168-949G>A		intron_variant	Intron 6 of 6	1		ENSP00000474083.2
OAS1	ENST00000552526.2	c.1083-949G>A		intron_variant	Intron 6 of 6	1		ENSP00000475139.2
OAS1	ENST00000551241.6	c.1039-949G>A		intron_variant	Intron 5 of 5	1		ENSP00000448790.1
ENSG00000257452	ENST00000552784.1	n.354-22251C>T		intron_variant	Intron 1 of 2	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

African (AFR) AF: 0.0325 AC: 1351 AN: 41528

American (AMR) AF: 0.0923 AC: 1411 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0590 AC: 205 AN: 3472

East Asian (EAS) AF: 0.313 AC: 1610 AN: 5150

South Asian (SAS) AF: 0.113 AC: 544 AN: 4824

European-Finnish (FIN) AF: 0.114 AC: 1205 AN: 10592

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0499 AC: 3390 AN: 68000

Other (OTH) AF: 0.0644 AC: 136 AN: 2112

Alfa AF: 0.0545 Hom.: 558

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
PhyloP100		-0.26
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs3803057; hg19: chr12-113368734;