rs7135577

Variant names:

• chr12-112920301-A-G
• rs7135577
• ENST00000540589.3:c.1167+686A>G

Your query was ambiguous. Multiple possible variants found:

• chr12-112920301-A-G
• chr12-112920301-A-T

Variant summary

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

The ENST00000540589.3(OAS1):​c.1167+686A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.752 in 152,174 control chromosomes in the GnomAD database, including 44,167 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 (44167 hom., cov: 33)
• Consequence: OAS1 ENST00000540589.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0410
• Publications: 15 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.923 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OAS1	NM_001320151.2	c.1038+2601A>G		intron_variant	Intron 5 of 5		NP_001307080.1
OAS1	NM_001406025.1	c.1014+2601A>G		intron_variant	Intron 5 of 5		NP_001392954.1
OAS1	NR_175991.1	n.1343+686A>G		intron_variant	Intron 6 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OAS1	ENST00000540589.3	c.1167+686A>G		intron_variant	Intron 6 of 6	1		ENSP00000474083.2
OAS1	ENST00000552526.2	c.1082+869A>G		intron_variant	Intron 6 of 6	1		ENSP00000475139.2
OAS1	ENST00000551241.6	c.1038+2601A>G		intron_variant	Intron 5 of 5	1		ENSP00000448790.1
ENSG00000257452	ENST00000552784.1	n.354-11623T>C		intron_variant	Intron 1 of 2	4

Frequencies

GnomAD3 genomes AF: 0.752 AC: 114285 AN: 152056 Hom.: 44102 Cov.: 33

Gnomad AFR AF: 0.931

Gnomad AMI AF: 0.684

Gnomad AMR AF: 0.767

Gnomad ASJ AF: 0.502

Gnomad EAS AF: 0.775

Gnomad SAS AF: 0.710

Gnomad FIN AF: 0.729

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.705

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

GnomAD4 genome AF: 0.752 AC: 114414 AN: 152174 Hom.: 44167 Cov.: 33 AF XY: 0.754 AC XY: 56066 AN XY: 74364

African (AFR) AF: 0.931 AC: 38685 AN: 41550

American (AMR) AF: 0.767 AC: 11736 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.502 AC: 1743 AN: 3472

East Asian (EAS) AF: 0.775 AC: 4016 AN: 5182

South Asian (SAS) AF: 0.710 AC: 3421 AN: 4820

European-Finnish (FIN) AF: 0.729 AC: 7700 AN: 10556

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.659 AC: 44823 AN: 67988

Other (OTH) AF: 0.708 AC: 1493 AN: 2108

Alfa AF: 0.717 Hom.: 4931

Bravo AF: 0.765

Asia WGS AF: 0.767 AC: 2667 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.1
DANN	Benign	0.70
PhyloP100		0.041
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: rs7135577; hg19: chr12-113358106;