NM_016816.4:c.180+143A>C

Variant names:

• chr12-112907362-A-C
• rs7956880
• NM_016816.4:c.180+143A>C

Variant summary

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

The NM_016816.4(OAS1):​c.180+143A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.812 in 696,950 control chromosomes in the GnomAD database, including 231,987 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.85 (55185 hom., cov: 31)
  • Exomes 𝑓: 0.80 (176802 hom.)
• Consequence: OAS1 NM_016816.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00100
• Publications: 6 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)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 12-112907362-A-C is Benign according to our data. Variant chr12-112907362-A-C is described in ClinVar as Benign. ClinVar VariationId is 1269600.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.97 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016816.4. 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	NM_016816.4	MANE Select	c.180+143A>C		intron	N/A	NP_058132.2
	OAS1	NM_001032409.3		c.180+143A>C		intron	N/A	NP_001027581.1
	OAS1	NM_001406020.1		c.180+143A>C		intron	N/A	NP_001392949.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OAS1	ENST00000202917.10	TSL:1 MANE Select	c.180+143A>C		intron	N/A	ENSP00000202917.5
	OAS1	ENST00000445409.7	TSL:1	c.180+143A>C		intron	N/A	ENSP00000388001.2
	OAS1	ENST00000540589.3	TSL:1	c.180+143A>C		intron	N/A	ENSP00000474083.2

Frequencies

GnomAD3 genomes AF: 0.847 AC: 128777 AN: 152052 Hom.: 55136 Cov.: 31

Gnomad AFR AF: 0.964

Gnomad AMI AF: 0.765

Gnomad AMR AF: 0.852

Gnomad ASJ AF: 0.675

Gnomad EAS AF: 0.993

Gnomad SAS AF: 0.776

Gnomad FIN AF: 0.796

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.787

Gnomad OTH AF: 0.837

GnomAD4 exome AF: 0.802 AC: 436970 AN: 544780 Hom.: 176802 AF XY: 0.799 AC XY: 226119 AN XY: 283136

African (AFR) AF: 0.965 AC: 13872 AN: 14376

American (AMR) AF: 0.837 AC: 16402 AN: 19598

Ashkenazi Jewish (ASJ) AF: 0.692 AC: 9800 AN: 14172

East Asian (EAS) AF: 0.987 AC: 31622 AN: 32052

South Asian (SAS) AF: 0.760 AC: 34879 AN: 45878

European-Finnish (FIN) AF: 0.793 AC: 34758 AN: 43842

Middle Eastern (MID) AF: 0.711 AC: 1515 AN: 2132

European-Non Finnish (NFE) AF: 0.787 AC: 270669 AN: 343808

Other (OTH) AF: 0.811 AC: 23453 AN: 28922

GnomAD4 genome AF: 0.847 AC: 128890 AN: 152170 Hom.: 55185 Cov.: 31 AF XY: 0.846 AC XY: 62929 AN XY: 74390

African (AFR) AF: 0.964 AC: 40040 AN: 41522

American (AMR) AF: 0.852 AC: 13026 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.675 AC: 2340 AN: 3468

East Asian (EAS) AF: 0.993 AC: 5149 AN: 5186

South Asian (SAS) AF: 0.776 AC: 3732 AN: 4812

European-Finnish (FIN) AF: 0.796 AC: 8426 AN: 10592

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.787 AC: 53496 AN: 67982

Other (OTH) AF: 0.839 AC: 1770 AN: 2110

Alfa AF: 0.830 Hom.: 9390

Bravo AF: 0.860

Asia WGS AF: 0.881 AC: 3064 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 13, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	9.0
DANN	Benign	0.85
PhyloP100		-0.0010
PromoterAI		0.038	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs7956880; hg19: chr12-113345167;