Genetic Variant NM_003733.4:c.1509G>A (chr12-121020597-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_003733.4(OASL):c.1509G>A(p.Ser503Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 1,607,120 control chromosomes in the GnomAD database, including 25,088 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 0.14 ( 1780 hom., cov: 32)

Exomes 𝑓: 0.17 ( 23308 hom. )

Consequence

OASL
NM_003733.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.509

Publications

37 publications found

Variant links:

Genes affected

OASL (HGNC:8090): (2'-5'-oligoadenylate synthetase like) Enables DNA binding activity and double-stranded RNA binding activity. Involved in several processes, including interleukin-27-mediated signaling pathway; negative regulation of viral genome replication; and positive regulation of RIG-I signaling pathway. Located in cytosol; nucleolus; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

OASL links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP7

Synonymous conserved (PhyloP=0.509 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OASL	NM_003733.4 link	c.1509G>A	p.Ser503Ser	synonymous_variant	Exon 6 of 6	ENST00000257570.10	NP_003724.1	Q15646-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OASL	ENST00000257570.10 link	c.1509G>A	p.Ser503Ser	synonymous_variant	Exon 6 of 6	1	NM_003733.4	ENSP00000257570.4		Q15646-1

Frequencies

GnomAD3 genomes

AF:

0.135

AC:

20571

AN:

152118

Hom.:

1779

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0485

Gnomad AMI

AF:

0.228

Gnomad AMR

AF:

0.0820

Gnomad ASJ

AF:

0.123

Gnomad EAS

AF:

0.125

Gnomad SAS

AF:

0.157

Gnomad FIN

AF:

0.190

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.191

Gnomad OTH

AF:

0.116

GnomAD2 exomes

AF:

0.149

AC:

37183

AN:

250174

AF XY:

0.154

show subpopulations

Gnomad AFR exome

AF:

0.0442

Gnomad AMR exome

AF:

0.0592

Gnomad ASJ exome

AF:

0.120

Gnomad EAS exome

AF:

0.122

Gnomad FIN exome

AF:

0.199

Gnomad NFE exome

AF:

0.183

Gnomad OTH exome

AF:

0.149

GnomAD4 exome

AF:

0.175

AC:

254034

AN:

1454884

Hom.:

23308

Cov.:

AF XY:

0.175

AC XY:

126470

AN XY:

722342

show subpopulations

African (AFR)

AF:

0.0425

AC:

1413

AN:

33274

American (AMR)

AF:

0.0639

AC:

2833

AN:

44336

Ashkenazi Jewish (ASJ)

AF:

0.120

AC:

3120

AN:

25988

East Asian (EAS)

AF:

0.105

AC:

4132

AN:

39492

South Asian (SAS)

AF:

0.165

AC:

14223

AN:

86032

European-Finnish (FIN)

AF:

0.192

AC:

10226

AN:

53368

Middle Eastern (MID)

AF:

0.108

AC:

621

AN:

5736

European-Non Finnish (NFE)

AF:

0.188

AC:

207720

AN:

1106640

Other (OTH)

AF:

0.162

AC:

9746

AN:

60018

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

10622

21245

31867

42490

53112

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7066

14132

21198

28264

35330

<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:

0.135

AC:

20577

AN:

152236

Hom.:

1780

Cov.:

AF XY:

0.136

AC XY:

10133

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.0484

AC:

2011

AN:

41568

American (AMR)

AF:

0.0819

AC:

1251

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.123

AC:

426

AN:

3472

East Asian (EAS)

AF:

0.126

AC:

650

AN:

5174

South Asian (SAS)

AF:

0.158

AC:

763

AN:

4828

European-Finnish (FIN)

AF:

0.190

AC:

2009

AN:

10588

Middle Eastern (MID)

AF:

0.0748

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.191

AC:

12994

AN:

68004

Other (OTH)

AF:

0.115

AC:

243

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

871

1742

2612

3483

4354

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

252

504

756

1008

1260

<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:

0.168

Hom.:

11088

Bravo

AF:

0.120

Asia WGS

AF:

0.0980

AC:

340

AN:

3478

EpiCase

AF:

0.185

EpiControl

AF:

0.180

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

5.2

(source)

DANN

Benign

0.40

PhyloP100

0.51

Mutation Taster

=100/0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over