12-112931954-G-C

Variant names:

• chr12-112931954-G-C
• rs7967461
• ENST00000540589.3:c.*32G>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000540589.3(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 ENST00000540589.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.365
• Publications: 22 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.009).
• BP6: Variant 12-112931954-G-C is Benign according to our data. Variant chr12-112931954-G-C is described in ClinVar as Benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000540589.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OAS1	NR_175991.1		n.1420G>C		non_coding_transcript_exon	Exon 7 of 7
	OAS1	NM_001320151.2		c.*32G>C		3_prime_UTR	Exon 6 of 6	NP_001307080.1
	OAS1	NM_001406025.1		c.*32G>C		3_prime_UTR	Exon 6 of 6	NP_001392954.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OAS1	ENST00000540589.3	TSL:1	c.*32G>C		3_prime_UTR	Exon 7 of 7	ENSP00000474083.2
	OAS1	ENST00000552526.2	TSL:1	c.*73G>C		3_prime_UTR	Exon 7 of 7	ENSP00000475139.2
	OAS1	ENST00000551241.6	TSL:1	c.*32G>C		3_prime_UTR	Exon 6 of 6	ENSP00000448790.1

Frequencies

GnomAD3 genomes AF: 0.741 AC: 112619 AN: 151962 Hom.: 42963 Cov.: 32

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

GnomAD2 exomes AF: 0.698 AC: 94770 AN: 135748 AF XY: 0.690

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 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.: 0 AF XY: 0.672 AC XY: 199397 AN XY: 296684

African (AFR) AF: 0.923 AC: 14385 AN: 15580

American (AMR) AF: 0.802 AC: 27655 AN: 34476

Ashkenazi Jewish (ASJ) AF: 0.508 AC: 10120 AN: 19902

East Asian (EAS) AF: 0.801 AC: 25632 AN: 31988

South Asian (SAS) AF: 0.692 AC: 43074 AN: 62216

European-Finnish (FIN) AF: 0.725 AC: 24306 AN: 33536

Middle Eastern (MID) AF: 0.583 AC: 2335 AN: 4002

European-Non Finnish (NFE) AF: 0.640 AC: 202046 AN: 315758

Other (OTH) AF: 0.670 AC: 20411 AN: 30476

GnomAD4 genome AF: 0.741 AC: 112741 AN: 152080 Hom.: 43022 Cov.: 32 AF XY: 0.745 AC XY: 55337 AN XY: 74324

African (AFR) AF: 0.927 AC: 38483 AN: 41510

American (AMR) AF: 0.750 AC: 11458 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1731 AN: 3462

East Asian (EAS) AF: 0.776 AC: 4018 AN: 5180

South Asian (SAS) AF: 0.709 AC: 3415 AN: 4820

European-Finnish (FIN) AF: 0.727 AC: 7672 AN: 10548

Middle Eastern (MID) AF: 0.592 AC: 173 AN: 292

European-Non Finnish (NFE) AF: 0.644 AC: 43762 AN: 67972

Other (OTH) AF: 0.694 AC: 1464 AN: 2108

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.1
DANN	Benign	0.71
PhyloP100		0.36
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs7967461; hg19: chr12-113369759; COSMIC: COSV73345157;