rs60623134

Positions:

• chr12-112918230-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000202917.10(OAS1):​c.1038+530A>G variant causes a intron 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 ENST00000202917.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OAS1	NM_016816.4	c.1038+530A>G		intron_variant		ENST00000202917.10	NP_058132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OAS1	ENST00000202917.10	c.1038+530A>G		intron_variant		1	NM_016816.4	ENSP00000202917	P2
	ENST00000552784.1	n.354-9552T>C		intron_variant, non_coding_transcript_variant		4

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

Gnomad4 AFR exome AF: 0.0170

Gnomad4 AMR exome AF: 0.0551

Gnomad4 ASJ exome AF: 0.0457

Gnomad4 EAS exome AF: 0.0664

Gnomad4 SAS exome AF: 0.0389

Gnomad4 FIN exome AF: 0.0594

Gnomad4 NFE exome AF: 0.0919

Gnomad4 OTH exome AF: 0.0985

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

Gnomad4 AFR AF: 0.0292

Gnomad4 AMR AF: 0.0758

Gnomad4 ASJ AF: 0.0643

Gnomad4 EAS AF: 0.0961

Gnomad4 SAS AF: 0.0585

Gnomad4 FIN AF: 0.0686

Gnomad4 NFE AF: 0.113

Gnomad4 OTH AF: 0.0875

Alfa AF: 0.0877 Hom.: 75

Bravo AF: 0.0774

Asia WGS AF: 0.102 AC: 356 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.9
DANN	Benign	0.82

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

Publications

LitVar

Other links and lift over

dbSNP: rs60623134; hg19: chr12-113356035;