rs7135579

chr12-112929077-C-T

Variant summary

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

The ENST00000540589.3(OAS1):c.1168-2801C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0661 in 152,298 control chromosomes in the GnomAD database, including 461 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 0.066 (461 hom., cov: 33)
• Consequence: OAS1 ENST00000540589.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.262

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=-0.69).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OAS1	NM_001320151.2	c.1039-2801C>T		intron_variant
OAS1	NM_001406025.1	c.1015-2801C>T		intron_variant
OAS1	NR_175991.1	n.1344-2801C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OAS1	ENST00000540589.3	c.1168-2801C>T		intron_variant		1
OAS1	ENST00000551241.6	c.1039-2801C>T		intron_variant		1
OAS1	ENST00000552526.2	c.1083-2801C>T		intron_variant		1		A2
	ENST00000552784.1	n.354-20399G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0662 AC: 10075 AN: 152180 Hom.: 463 Cov.: 33

Gnomad AFR AF: 0.0179

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.0601

Gnomad ASJ AF: 0.0617

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0112

Gnomad FIN AF: 0.0587

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.0674

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

GnomAD4 genome AF: 0.0661 AC: 10067 AN: 152298 Hom.: 461 Cov.: 33 AF XY: 0.0611 AC XY: 4548 AN XY: 74484

Gnomad4 AFR AF: 0.0178

Gnomad4 AMR AF: 0.0599

Gnomad4 ASJ AF: 0.0617

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0108

Gnomad4 FIN AF: 0.0587

Gnomad4 NFE AF: 0.107

Gnomad4 OTH AF: 0.0662

Alfa AF: 0.0874 Hom.: 299

Bravo AF: 0.0649

Asia WGS AF: 0.0110 AC: 41 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
Cadd	Benign	5.5
Dann	Benign	0.85

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7135579; hg19: chr12-113366882;