rs7956880

chr12-112907362-A-C

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.180+143A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.812 in 696,950 control chromosomes in the GnomAD database, including 231,987 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.85 (55185 hom., cov: 31)
  • Exomes 𝑓: 0.80 (176802 hom.)
• Consequence: OAS1 NM_016816.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00100

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 12-112907362-A-C is Benign according to our data. Variant chr12-112907362-A-C is described in ClinVar as [Benign]. Clinvar id is 1269600.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.97 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OAS1	NM_016816.4	c.180+143A>C		intron_variant		ENST00000202917.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OAS1	ENST00000202917.10	c.180+143A>C		intron_variant		1	NM_016816.4	P2

Frequencies

GnomAD3 genomes AF: 0.847 AC: 128777 AN: 152052 Hom.: 55136 Cov.: 31

Gnomad AFR AF: 0.964

Gnomad AMI AF: 0.765

Gnomad AMR AF: 0.852

Gnomad ASJ AF: 0.675

Gnomad EAS AF: 0.993

Gnomad SAS AF: 0.776

Gnomad FIN AF: 0.796

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.787

Gnomad OTH AF: 0.837

GnomAD4 exome AF: 0.802 AC: 436970 AN: 544780 Hom.: 176802 AF XY: 0.799 AC XY: 226119 AN XY: 283136

Gnomad4 AFR exome AF: 0.965

Gnomad4 AMR exome AF: 0.837

Gnomad4 ASJ exome AF: 0.692

Gnomad4 EAS exome AF: 0.987

Gnomad4 SAS exome AF: 0.760

Gnomad4 FIN exome AF: 0.793

Gnomad4 NFE exome AF: 0.787

Gnomad4 OTH exome AF: 0.811

GnomAD4 genome AF: 0.847 AC: 128890 AN: 152170 Hom.: 55185 Cov.: 31 AF XY: 0.846 AC XY: 62929 AN XY: 74390

Gnomad4 AFR AF: 0.964

Gnomad4 AMR AF: 0.852

Gnomad4 ASJ AF: 0.675

Gnomad4 EAS AF: 0.993

Gnomad4 SAS AF: 0.776

Gnomad4 FIN AF: 0.796

Gnomad4 NFE AF: 0.787

Gnomad4 OTH AF: 0.839

Alfa AF: 0.830 Hom.: 9390

Bravo AF: 0.860

Asia WGS AF: 0.881 AC: 3064 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 13, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	9.0
Dann	Benign	0.85

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: rs7956880; hg19: chr12-113345167;