NM_016816.4:c.470-195C>T

Variant names:

• chr12-112910856-C-T
• rs34137742
• NM_016816.4:c.470-195C>T

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.470-195C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 151,952 control chromosomes in the GnomAD database, including 1,526 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.13 (1526 hom., cov: 31)
• Consequence: OAS1 NM_016816.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.54
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 12-112910856-C-T is Benign according to our data. Variant chr12-112910856-C-T is described in ClinVar as Benign. ClinVar VariationId is 1221922.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.208 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.470-195C>T		intron	N/A	NP_058132.2
	OAS1	NM_001032409.3		c.470-195C>T		intron	N/A	NP_001027581.1
	OAS1	NM_001406020.1		c.470-242C>T		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.470-195C>T		intron	N/A	ENSP00000202917.5
	OAS1	ENST00000445409.7	TSL:1	c.470-195C>T		intron	N/A	ENSP00000388001.2
	OAS1	ENST00000540589.3	TSL:1	c.470-195C>T		intron	N/A	ENSP00000474083.2

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19739 AN: 151834 Hom.: 1521 Cov.: 31

Gnomad AFR AF: 0.0764

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.0328

Gnomad SAS AF: 0.0980

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.130 AC: 19752 AN: 151952 Hom.: 1526 Cov.: 31 AF XY: 0.130 AC XY: 9661 AN XY: 74278

African (AFR) AF: 0.0765 AC: 3170 AN: 41462

American (AMR) AF: 0.214 AC: 3264 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 479 AN: 3470

East Asian (EAS) AF: 0.0325 AC: 168 AN: 5170

South Asian (SAS) AF: 0.0978 AC: 469 AN: 4794

European-Finnish (FIN) AF: 0.134 AC: 1416 AN: 10562

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.152 AC: 10309 AN: 67932

Other (OTH) AF: 0.138 AC: 291 AN: 2104

Alfa AF: 0.122 Hom.: 540

Bravo AF: 0.135

Asia WGS AF: 0.0820 AC: 284 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.11
DANN	Benign	0.43
PhyloP100		-1.5
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: rs34137742; hg19: chr12-113348661;