dbSNP rs3213545: OASL:p.Leu136Leu (chr12-121033534-G-A) – 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.408C>T(p.Leu136Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 1,613,822 control chromosomes in the GnomAD database, including 73,977 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 0.27 ( 5856 hom., cov: 31)

Exomes 𝑓: 0.30 ( 68121 hom. )

Consequence

OASL
NM_003733.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.545

Publications

64 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:

Genome browser will be placed here

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=-0.87).

BP7

Synonymous conserved (PhyloP=-0.545 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OASL	NM_003733.4 link	c.408C>T	p.Leu136Leu	synonymous_variant	Exon 2 of 6	ENST00000257570.10	NP_003724.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OASL	ENST00000257570.10 link	c.408C>T	p.Leu136Leu	synonymous_variant	Exon 2 of 6	1	NM_003733.4	ENSP00000257570.4

Frequencies

GnomAD3 genomes

AF:

0.265

AC:

40271

AN:

151880

Hom.:

5854

Cov.:

show subpopulations

Gnomad AFR

AF:

0.148

Gnomad AMI

AF:

0.382

Gnomad AMR

AF:

0.270

Gnomad ASJ

AF:

0.430

Gnomad EAS

AF:

0.476

Gnomad SAS

AF:

0.414

Gnomad FIN

AF:

0.312

Gnomad MID

AF:

0.497

Gnomad NFE

AF:

0.289

Gnomad OTH

AF:

0.286

GnomAD2 exomes

AF:

0.316

AC:

79298

AN:

250948

AF XY:

0.325

show subpopulations

Gnomad AFR exome

AF:

0.141

Gnomad AMR exome

AF:

0.255

Gnomad ASJ exome

AF:

0.431

Gnomad EAS exome

AF:

0.478

Gnomad FIN exome

AF:

0.302

Gnomad NFE exome

AF:

0.297

Gnomad OTH exome

AF:

0.318

GnomAD4 exome

AF:

0.299

AC:

437705

AN:

1461824

Hom.:

68121

Cov.:

AF XY:

0.304

AC XY:

221180

AN XY:

727214

show subpopulations

African (AFR)

AF:

0.146

AC:

4873

AN:

33480

American (AMR)

AF:

0.257

AC:

11486

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.435

AC:

11371

AN:

26136

East Asian (EAS)

AF:

0.504

AC:

20016

AN:

39700

South Asian (SAS)

AF:

0.417

AC:

35928

AN:

86256

European-Finnish (FIN)

AF:

0.300

AC:

16012

AN:

53418

Middle Eastern (MID)

AF:

0.450

AC:

2597

AN:

5768

European-Non Finnish (NFE)

AF:

0.285

AC:

316609

AN:

1111958

Other (OTH)

AF:

0.312

AC:

18813

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

18712

37424

56135

74847

93559

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10598

21196

31794

42392

52990

<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:

0.265

AC:

40280

AN:

151998

Hom.:

5856

Cov.:

AF XY:

0.271

AC XY:

20148

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.148

AC:

6159

AN:

41486

American (AMR)

AF:

0.270

AC:

4123

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.430

AC:

1491

AN:

3470

East Asian (EAS)

AF:

0.476

AC:

2440

AN:

5128

South Asian (SAS)

AF:

0.413

AC:

1991

AN:

4824

European-Finnish (FIN)

AF:

0.312

AC:

3302

AN:

10578

Middle Eastern (MID)

AF:

0.486

AC:

143

AN:

294

European-Non Finnish (NFE)

AF:

0.289

AC:

19666

AN:

67942

Other (OTH)

AF:

0.293

AC:

617

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1516

3033

4549

6066

7582

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

436

872

1308

1744

2180

<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:

0.278

Hom.:

18275

Bravo

AF:

0.253

Asia WGS

AF:

0.424

AC:

1471

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.32

(source)

DANN

Benign

0.41

PhyloP100

-0.55

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