rs60623134

Variant names:

• chr12-112918230-A-G
• rs60623134
• ENST00000452357.7:c.*473A>G

Variant summary

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

The NM_001406024.1(OAS1):​c.*473A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0788 in 195,484 control chromosomes in the GnomAD database, including 743 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 0.080 (574 hom., cov: 32)
  • Exomes 𝑓: 0.076 (169 hom.)
• Consequence: OAS1 NM_001406024.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347
• Publications: 2 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001406024.1. 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.1038+530A>G		intron	N/A	NP_058132.2
	OAS1	NM_001406024.1		c.*473A>G		3_prime_UTR	Exon 5 of 5	NP_001392953.1
	OAS1	NM_001406030.1		c.*473A>G		3_prime_UTR	Exon 3 of 3	NP_001392959.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OAS1	ENST00000452357.7	TSL:1	c.*473A>G		3_prime_UTR	Exon 5 of 5	ENSP00000415721.2
	OAS1	ENST00000202917.10	TSL:1 MANE Select	c.1038+530A>G		intron	N/A	ENSP00000202917.5
	OAS1	ENST00000445409.7	TSL:1	c.1038+530A>G		intron	N/A	ENSP00000388001.2

Frequencies

GnomAD3 genomes AF: 0.0797 AC: 12110 AN: 151956 Hom.: 577 Cov.: 32

Gnomad AFR AF: 0.0293

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.0760

Gnomad ASJ AF: 0.0643

Gnomad EAS AF: 0.0958

Gnomad SAS AF: 0.0591

Gnomad FIN AF: 0.0686

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.0874

GnomAD4 exome AF: 0.0762 AC: 3307 AN: 43410 Hom.: 169 Cov.: 0 AF XY: 0.0743 AC XY: 1699 AN XY: 22856

African (AFR) AF: 0.0170 AC: 14 AN: 824

American (AMR) AF: 0.0551 AC: 189 AN: 3428

Ashkenazi Jewish (ASJ) AF: 0.0457 AC: 39 AN: 854

East Asian (EAS) AF: 0.0664 AC: 138 AN: 2078

South Asian (SAS) AF: 0.0389 AC: 257 AN: 6606

European-Finnish (FIN) AF: 0.0594 AC: 103 AN: 1734

Middle Eastern (MID) AF: 0.0321 AC: 5 AN: 156

European-Non Finnish (NFE) AF: 0.0919 AC: 2355 AN: 25628

Other (OTH) AF: 0.0985 AC: 207 AN: 2102

GnomAD4 genome AF: 0.0796 AC: 12101 AN: 152074 Hom.: 574 Cov.: 32 AF XY: 0.0758 AC XY: 5638 AN XY: 74354

African (AFR) AF: 0.0292 AC: 1210 AN: 41484

American (AMR) AF: 0.0758 AC: 1157 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.0643 AC: 223 AN: 3470

East Asian (EAS) AF: 0.0961 AC: 497 AN: 5174

South Asian (SAS) AF: 0.0585 AC: 282 AN: 4820

European-Finnish (FIN) AF: 0.0686 AC: 726 AN: 10580

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7678 AN: 67974

Other (OTH) AF: 0.0875 AC: 184 AN: 2104

Alfa AF: 0.0696 Hom.: 163

Bravo AF: 0.0774

Asia WGS AF: 0.102 AC: 356 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.9
DANN	Benign	0.82
PhyloP100		0.35
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: rs60623134; hg19: chr12-113356035;