rs34137742

Positions:

• chr12-112910856-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OAS1	NM_016816.4	c.470-195C>T		intron_variant		ENST00000202917.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OAS1	ENST00000202917.10	c.470-195C>T		intron_variant		1	NM_016816.4	P2
	ENST00000552784.1	n.354-2178G>A		intron_variant, non_coding_transcript_variant		4

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

Gnomad4 AFR AF: 0.0765

Gnomad4 AMR AF: 0.214

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.0325

Gnomad4 SAS AF: 0.0978

Gnomad4 FIN AF: 0.134

Gnomad4 NFE AF: 0.152

Gnomad4 OTH AF: 0.138

Alfa AF: 0.135 Hom.: 236

Bravo AF: 0.135

Asia WGS AF: 0.0820 AC: 284 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.11
DANN	Benign	0.43

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: rs34137742; hg19: chr12-113348661;