12-112907451-C-G

Variant names:

• chr12-112907451-C-G
• rs10744785
• NM_016816.4:c.180+232C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016816.4(OAS1):​c.180+232C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.7 in 152,194 control chromosomes in the GnomAD database, including 39,134 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.70 (39134 hom., cov: 33)
• Consequence: OAS1 NM_016816.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.368
• Publications: 12 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OAS1	NM_016816.4	MANE Select	c.180+232C>G		intron	N/A	NP_058132.2	P00973-1
	OAS1	NM_001032409.3		c.180+232C>G		intron	N/A	NP_001027581.1	P00973-3
	OAS1	NM_001406020.1		c.180+232C>G		intron	N/A	NP_001392949.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OAS1	ENST00000202917.10	TSL:1 MANE Select	c.180+232C>G		intron	N/A	ENSP00000202917.5	P00973-1
	OAS1	ENST00000445409.7	TSL:1	c.180+232C>G		intron	N/A	ENSP00000388001.2	P00973-3
	OAS1	ENST00000540589.3	TSL:1	c.180+232C>G		intron	N/A	ENSP00000474083.2	S4R3A5

Frequencies

GnomAD3 genomes AF: 0.701 AC: 106578 AN: 152076 Hom.: 39139 Cov.: 33

Gnomad AFR AF: 0.466

Gnomad AMI AF: 0.765

Gnomad AMR AF: 0.789

Gnomad ASJ AF: 0.630

Gnomad EAS AF: 0.993

Gnomad SAS AF: 0.771

Gnomad FIN AF: 0.796

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.784

Gnomad OTH AF: 0.728

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.700 AC: 106611 AN: 152194 Hom.: 39134 Cov.: 33 AF XY: 0.705 AC XY: 52491 AN XY: 74414

African (AFR) AF: 0.466 AC: 19335 AN: 41482

American (AMR) AF: 0.788 AC: 12066 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.630 AC: 2187 AN: 3470

East Asian (EAS) AF: 0.993 AC: 5146 AN: 5184

South Asian (SAS) AF: 0.771 AC: 3720 AN: 4826

European-Finnish (FIN) AF: 0.796 AC: 8432 AN: 10596

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.784 AC: 53302 AN: 68014

Other (OTH) AF: 0.725 AC: 1533 AN: 2114

Alfa AF: 0.670 Hom.: 2196

Bravo AF: 0.692

Asia WGS AF: 0.811 AC: 2819 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.24
DANN	Benign	0.36
PhyloP100		-0.37
PromoterAI		-0.029	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: rs10744785; hg19: chr12-113345256;