rs11352835

Positions:

• chr12-112931910-TA-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM4 BP6_Moderate BA1

The ENST00000540589.3(OAS1):​c.1201del​(p.Thr401ProfsTer26) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.74 (42993 hom., cov: 0)
  • Exomes 𝑓: 0.68 (127347 hom.)
• Consequence: OAS1 ENST00000540589.3 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.554

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 -8 ACMG points.

• PM4: Frameshift in the end of transcript resulting in stoplost. Downstream stopcodon found after 427 codons.
• BP6: Variant 12-112931910-TA-T is Benign according to our data. Variant chr12-112931910-TA-T is described in ClinVar as [Benign]. Clinvar id is 3058877.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.919 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OAS1	NM_001320151.2	c.1072del	p.Thr358ProfsTer26	frameshift_variant	6/6
OAS1	NM_001406025.1	c.1048del	p.Thr350ProfsTer26	frameshift_variant	6/6
OAS1	NR_175991.1	n.1377del		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OAS1	ENST00000540589.3	c.1201del	p.Thr401ProfsTer26	frameshift_variant	7/7	1
OAS1	ENST00000551241.6	c.1072del	p.Thr358ProfsTer26	frameshift_variant	6/6	1
OAS1	ENST00000552526.2	c.*30del		3_prime_UTR_variant	7/7	1		A2
	ENST00000552784.1	n.354-23233del		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.741 AC: 112568 AN: 151936 Hom.: 42934 Cov.: 0

Gnomad AFR AF: 0.927

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.750

Gnomad ASJ AF: 0.499

Gnomad EAS AF: 0.775

Gnomad SAS AF: 0.709

Gnomad FIN AF: 0.726

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.644

Gnomad OTH AF: 0.689

GnomAD3 exomes AF: 0.699 AC: 95544 AN: 136774 Hom.: 34251 AF XY: 0.690 AC XY: 51071 AN XY: 74002

Gnomad AFR exome AF: 0.936

Gnomad AMR exome AF: 0.809

Gnomad ASJ exome AF: 0.500

Gnomad EAS exome AF: 0.793

Gnomad SAS exome AF: 0.691

Gnomad FIN exome AF: 0.731

Gnomad NFE exome AF: 0.636

Gnomad OTH exome AF: 0.652

GnomAD4 exome AF: 0.675 AC: 370471 AN: 548748 Hom.: 127347 Cov.: 0 AF XY: 0.672 AC XY: 199640 AN XY: 297064

Gnomad4 AFR exome AF: 0.923

Gnomad4 AMR exome AF: 0.802

Gnomad4 ASJ exome AF: 0.508

Gnomad4 EAS exome AF: 0.802

Gnomad4 SAS exome AF: 0.692

Gnomad4 FIN exome AF: 0.724

Gnomad4 NFE exome AF: 0.640

Gnomad4 OTH exome AF: 0.670

GnomAD4 genome AF: 0.741 AC: 112690 AN: 152054 Hom.: 42993 Cov.: 0 AF XY: 0.744 AC XY: 55301 AN XY: 74304

Gnomad4 AFR AF: 0.927

Gnomad4 AMR AF: 0.751

Gnomad4 ASJ AF: 0.499

Gnomad4 EAS AF: 0.775

Gnomad4 SAS AF: 0.709

Gnomad4 FIN AF: 0.726

Gnomad4 NFE AF: 0.644

Gnomad4 OTH AF: 0.692

Alfa AF: 0.538 Hom.: 3183

Bravo AF: 0.753

Asia WGS AF: 0.768 AC: 2671 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

OAS1-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11352835; hg19: chr12-113369715; COSMIC: COSV73345101;