rs10774671

chr12-112919388-G-Achr12-112919388-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_016816.4(OAS1):c.1039-1G>A variant causes a splice acceptor change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 1,598,136 control chromosomes in the GnomAD database, including 340,187 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.60 (28580 hom., cov: 32)
  • Exomes 𝑓: 0.65 (311607 hom.)
• Consequence: OAS1 NM_016816.4 splice_acceptor
• Scores: Splicing: ADA: 0.0007956
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.729

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_addAF=-0.802932).
• BP6: Variant 12-112919388-G-A is Benign according to our data. Variant chr12-112919388-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1156518.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-112919388-G-A is described in Lovd as [Likely_pathogenic].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.753 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OAS1	NM_016816.4	c.1039-1G>A		splice_acceptor_variant		ENST00000202917.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OAS1	ENST00000202917.10	c.1039-1G>A		splice_acceptor_variant		1	NM_016816.4	P2
	ENST00000552784.1	n.354-10710C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.601 AC: 91290 AN: 151964 Hom.: 28562 Cov.: 32

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.685

Gnomad AMR AF: 0.702

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.773

Gnomad SAS AF: 0.704

Gnomad FIN AF: 0.728

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.653

Gnomad OTH AF: 0.592

GnomAD3 exomes AF: 0.672 AC: 166967 AN: 248584 Hom.: 57604 AF XY: 0.672 AC XY: 90151 AN XY: 134228

Gnomad AFR exome AF: 0.417

Gnomad AMR exome AF: 0.793

Gnomad ASJ exome AF: 0.457

Gnomad EAS exome AF: 0.787

Gnomad SAS exome AF: 0.690

Gnomad FIN exome AF: 0.738

Gnomad NFE exome AF: 0.655

Gnomad OTH exome AF: 0.642

GnomAD4 exome AF: 0.651 AC: 941833 AN: 1446056 Hom.: 311607 Cov.: 38 AF XY: 0.652 AC XY: 469297 AN XY: 719562

Gnomad4 AFR exome AF: 0.401

Gnomad4 AMR exome AF: 0.783

Gnomad4 ASJ exome AF: 0.461

Gnomad4 EAS exome AF: 0.796

Gnomad4 SAS exome AF: 0.690

Gnomad4 FIN exome AF: 0.730

Gnomad4 NFE exome AF: 0.648

Gnomad4 OTH exome AF: 0.622

GnomAD4 genome AF: 0.601 AC: 91352 AN: 152080 Hom.: 28580 Cov.: 32 AF XY: 0.609 AC XY: 45280 AN XY: 74342

Gnomad4 AFR AF: 0.422

Gnomad4 AMR AF: 0.702

Gnomad4 ASJ AF: 0.457

Gnomad4 EAS AF: 0.773

Gnomad4 SAS AF: 0.705

Gnomad4 FIN AF: 0.728

Gnomad4 NFE AF: 0.653

Gnomad4 OTH AF: 0.591

Alfa AF: 0.632 Hom.: 64286

Bravo AF: 0.592

TwinsUK AF: 0.642 AC: 2381

ALSPAC AF: 0.658 AC: 2536

ESP6500AA AF: 0.435 AC: 1917

ESP6500EA AF: 0.638 AC: 5490

ExAC AF: 0.665 AC: 80727

Asia WGS AF: 0.699 AC: 2431 AN: 3478

EpiCase AF: 0.632

EpiControl AF: 0.638

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	This variant is associated with the following publications: (PMID: 29242559, 28640813, 15732009, 20679634, 19247438, 21173033, 15855350, 21182542) -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 92% of patients studied by a panel of primary immunodeficiencies. Number of patients: 87. Only high quality variants are reported. -

OAS1-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.78
Cadd	Benign	15
Dann	Benign	0.87
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.056	N
MutationTaster	Benign	0.39	P;P;P
GERP RS		2.9

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00080
dbscSNV1_RF	Benign	0.018
SpliceAI score (max)		0.10		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: rs10774671; hg19: chr12-113357193; COSMIC: COSV52539465; COSMIC: COSV52539465;