Genetic Variant OAS1:c.*32G>C (chr12-112931954-G-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001320151.2(OAS1):c.*32G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.69 in 700,014 control chromosomes in the GnomAD database, including 170,199 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.74 ( 43022 hom., cov: 32)

Exomes 𝑓: 0.68 ( 127177 hom. )

Consequence

OAS1
NM_001320151.2 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.365

Variant links:

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 links:

ENSG00000257452 (HGNC:):

ENSG00000257452 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 12-112931954-G-C is Benign according to our data. Variant chr12-112931954-G-C is described in ClinVar as [Benign]. Clinvar id is 2687938.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	Effect	Exon rank	Protein	UniProt
OAS1	NM_001320151.2 link	c.*32G>C	3_prime_UTR_variant	Exon 6 of 6	NP_001307080.1	P00973-4
OAS1	NM_001406025.1 link	c.*32G>C	3_prime_UTR_variant	Exon 6 of 6	NP_001392954.1
OAS1	NR_175991.1 link	n.1420G>C	non_coding_transcript_exon_variant	Exon 7 of 7

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
OAS1	ENST00000540589.3 link	c.*32G>C	3_prime_UTR_variant	Exon 7 of 7	1	ENSP00000474083.2	S4R3A5
OAS1	ENST00000552526.2 link	c.*73G>C	3_prime_UTR_variant	Exon 7 of 7	1	ENSP00000475139.2	S4R467
OAS1	ENST00000551241.6 link	c.*32G>C	3_prime_UTR_variant	Exon 6 of 6	1	ENSP00000448790.1	P00973-4
ENSG00000257452	ENST00000552784.1 link	n.354-23276C>G	intron_variant	Intron 1 of 2	4

Frequencies

GnomAD3 genomes

AF:

0.741

AC:

112619

AN:

151962

Hom.:

42963

Cov.:

show subpopulations

Gnomad AFR

AF:

0.927

Gnomad AMI

AF:

0.620

Gnomad AMR

AF:

0.750

Gnomad ASJ

AF:

0.500

Gnomad EAS

AF:

0.775

Gnomad SAS

AF:

0.709

Gnomad FIN

AF:

0.727

Gnomad MID

AF:

0.596

Gnomad NFE

AF:

0.644

Gnomad OTH

AF:

0.691

GnomAD3 exomes

AF:

0.698

AC:

94770

AN:

135748

Hom.:

33956

AF XY:

0.690

AC XY:

50856

AN XY:

73708

show subpopulations

Gnomad AFR exome

AF:

0.936

Gnomad AMR exome

AF:

0.808

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:

0.635

Gnomad OTH exome

AF:

0.650

GnomAD4 exome

AF:

0.675

AC:

369964

AN:

547934

Hom.:

127177

Cov.:

AF XY:

0.672

AC XY:

199397

AN XY:

296684

show subpopulations

Gnomad4 AFR exome

AF:

0.923

Gnomad4 AMR exome

AF:

0.802

Gnomad4 ASJ exome

AF:

0.508

Gnomad4 EAS exome

AF:

0.801

Gnomad4 SAS exome

AF:

0.692

Gnomad4 FIN exome

AF:

0.725

Gnomad4 NFE exome

AF:

0.640

Gnomad4 OTH exome

AF:

0.670

GnomAD4 genome

AF:

0.741

AC:

112741

AN:

152080

Hom.:

43022

Cov.:

AF XY:

0.745

AC XY:

55337

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.927

Gnomad4 AMR

AF:

0.750

Gnomad4 ASJ

AF:

0.500

Gnomad4 EAS

AF:

0.776

Gnomad4 SAS

AF:

0.709

Gnomad4 FIN

AF:

0.727

Gnomad4 NFE

AF:

0.644

Gnomad4 OTH

AF:

0.694

Alfa

AF:

0.581

Hom.:

2810

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

LINK: link

Submissions by phenotype

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 93% of patients studied by a panel of primary immunodeficiencies. Number of patients: 88. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

3.1

DANN

Benign

0.71

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over