dbSNP rs111889842: OAS1:c.-217G>A (chr12-112906823-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000445409.7(OAS1):c.-217G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00777 in 503,498 control chromosomes in the GnomAD database, including 139 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 103 hom., cov: 33)

Exomes 𝑓: 0.0030 ( 36 hom. )

Consequence

OAS1
ENST00000445409.7 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0910

Publications

0 publications found

Variant links:

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)

OAS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 12-112906823-G-A is Benign according to our data. Variant chr12-112906823-G-A is described in ClinVar as Benign. ClinVar VariationId is 1241792.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0623 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000445409.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
OAS1	NM_016816.4	MANE Select	c.-217G>A	upstream_gene	N/A	NP_058132.2	P00973-1
OAS1	NM_001032409.3		c.-217G>A	upstream_gene	N/A	NP_001027581.1	P00973-3
OAS1	NM_001406020.1		c.-217G>A	upstream_gene	N/A	NP_001392949.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
OAS1	ENST00000445409.7	TSL:1	c.-217G>A	5_prime_UTR	Exon 1 of 6	ENSP00000388001.2	P00973-3
OAS1	ENST00000452357.7	TSL:1	c.-217G>A	5_prime_UTR	Exon 1 of 5	ENSP00000415721.2	P00973-2
OAS1	ENST00000680189.1		c.-217G>A	5_prime_UTR	Exon 2 of 7	ENSP00000505572.1	P00973-1

Frequencies

GnomAD3 genomes

AF:

0.0187

AC:

2846

AN:

152192

Hom.:

103

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0644

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00831

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000367

Gnomad OTH

AF:

0.0105

GnomAD4 exome

AF:

0.00303

AC:

1064

AN:

351188

Hom.:

Cov.:

AF XY:

0.00272

AC XY:

493

AN XY:

181228

show subpopulations

African (AFR)

AF:

0.0637

AC:

717

AN:

11252

American (AMR)

AF:

0.00686

AC:

108

AN:

15752

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11296

East Asian (EAS)

AF:

0.00

AC:

AN:

27888

South Asian (SAS)

AF:

0.0000401

AC:

AN:

24942

European-Finnish (FIN)

AF:

0.00

AC:

AN:

25026

Middle Eastern (MID)

AF:

0.00558

AC:

AN:

1612

European-Non Finnish (NFE)

AF:

0.000387

AC:

AN:

211970

Other (OTH)

AF:

0.00685

AC:

147

AN:

21450

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

103

154

206

257

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0187

AC:

2850

AN:

152310

Hom.:

103

Cov.:

AF XY:

0.0183

AC XY:

1360

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.0643

AC:

2672

AN:

41552

American (AMR)

AF:

0.00830

AC:

127

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000367

AC:

AN:

68032

Other (OTH)

AF:

0.0104

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

137

274

410

547

684

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0255

Hom.:

Bravo

AF:

0.0218

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.4

(source)

DANN

Benign

0.48

PhyloP100

0.091

PromoterAI

-0.059

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over