rs7135577

chr12-112920301-A-Gchr12-112920301-A-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.91).
• 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/exons	MANE	UniProt
OAS1	NM_001320151.2	c.1038+2601A>G		intron_variant
OAS1	NM_001406025.1	c.1014+2601A>G		intron_variant
OAS1	NR_175991.1	n.1343+686A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OAS1	ENST00000540589.3	c.1167+686A>G		intron_variant		1
OAS1	ENST00000551241.6	c.1038+2601A>G		intron_variant		1
OAS1	ENST00000552526.2	c.1082+869A>G		intron_variant		1		A2
	ENST00000552784.1	n.354-11623T>C		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.931

Gnomad4 AMR AF: 0.767

Gnomad4 ASJ AF: 0.502

Gnomad4 EAS AF: 0.775

Gnomad4 SAS AF: 0.710

Gnomad4 FIN AF: 0.729

Gnomad4 NFE AF: 0.659

Gnomad4 OTH AF: 0.708

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7135577; hg19: chr12-113358106;