chr12-112931910-TA-T

Variant names:

• chr12-112931910-TA-T
• rs11352835
• ENST00000540589.3:c.1201delA

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6 BA1

The ENST00000540589.3(OAS1):​c.1201delA​(p.Thr401ProfsTer26) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.74 (42993 hom., cov: 0)
  • Exomes 𝑓: 0.68 (127347 hom.)
• Consequence: OAS1 ENST00000540589.3 frameshift
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.554
• Publications: 16 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 -9 ACMG points.

• BP6: Variant 12-112931910-TA-T is Benign according to our data. Variant chr12-112931910-TA-T is described in ClinVar as Benign. ClinVar VariationId is 3058877.Status of the report is no_assertion_criteria_provided, 0 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 rank	MANE	Protein	UniProt
OAS1	NM_001320151.2	c.1072delA	p.Thr358ProfsTer26	frameshift_variant	Exon 6 of 6		NP_001307080.1
OAS1	NM_001406025.1	c.1048delA	p.Thr350ProfsTer26	frameshift_variant	Exon 6 of 6		NP_001392954.1
OAS1	NR_175991.1	n.1377delA		non_coding_transcript_exon_variant	Exon 7 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OAS1	ENST00000540589.3	c.1201delA	p.Thr401ProfsTer26	frameshift_variant	Exon 7 of 7	1		ENSP00000474083.2
OAS1	ENST00000551241.6	c.1072delA	p.Thr358ProfsTer26	frameshift_variant	Exon 6 of 6	1		ENSP00000448790.1
OAS1	ENST00000552526.2	c.*30delA		3_prime_UTR_variant	Exon 7 of 7	1		ENSP00000475139.2
ENSG00000257452	ENST00000552784.1	n.354-23233delT		intron_variant	Intron 1 of 2	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

GnomAD2 exomes AF: 0.699 AC: 95544 AN: 136774 AF XY: 0.690

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 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

African (AFR) AF: 0.923 AC: 14393 AN: 15590

American (AMR) AF: 0.802 AC: 27682 AN: 34510

Ashkenazi Jewish (ASJ) AF: 0.508 AC: 10129 AN: 19922

East Asian (EAS) AF: 0.802 AC: 25653 AN: 32004

South Asian (SAS) AF: 0.692 AC: 43093 AN: 62264

European-Finnish (FIN) AF: 0.724 AC: 24450 AN: 33748

Middle Eastern (MID) AF: 0.586 AC: 2378 AN: 4060

European-Non Finnish (NFE) AF: 0.640 AC: 202175 AN: 316038

Other (OTH) AF: 0.670 AC: 20518 AN: 30612

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

African (AFR) AF: 0.927 AC: 38475 AN: 41502

American (AMR) AF: 0.751 AC: 11472 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.499 AC: 1734 AN: 3472

East Asian (EAS) AF: 0.775 AC: 4000 AN: 5158

South Asian (SAS) AF: 0.709 AC: 3415 AN: 4818

European-Finnish (FIN) AF: 0.726 AC: 7660 AN: 10550

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.644 AC: 43739 AN: 67962

Other (OTH) AF: 0.692 AC: 1456 AN: 2104

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: no assertion criteria provided

Submissions by phenotype

OAS1-related disorder Benign:1

May 17, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.55
Mutation Taster		=175/25	polymorphism

Splicing

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

Other links and lift over

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