Genetic Variant OSR1:p.Leu218Leu (chr2-19353152-C-T) – 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 NM_145260.3(OSR1):c.654G>A(p.Leu218Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0509 in 1,613,510 control chromosomes in the GnomAD database, including 4,467 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1791 hom., cov: 33)

Exomes 𝑓: 0.045 ( 2676 hom. )

Consequence

OSR1
NM_145260.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.355

Publications

13 publications found

Variant links:

Genes affected

OSR1 (HGNC:8111): (odd-skipped related transcription factor 1) Enables sequence-specific double-stranded DNA binding activity. Involved in negative regulation of ion transmembrane transporter activity; positive regulation of gastrulation; and pronephros development. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

OSR1 links:

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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=-0.58).

BP6

Variant 2-19353152-C-T is Benign according to our data. Variant chr2-19353152-C-T is described in ClinVar as [Benign]. Clinvar id is 1227593.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OSR1	NM_145260.3 link	c.654G>A	p.Leu218Leu	synonymous_variant	Exon 2 of 3	ENST00000272223.3	NP_660303.1	Q8TAX0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OSR1	ENST00000272223.3 link	c.654G>A	p.Leu218Leu	synonymous_variant	Exon 2 of 3	1	NM_145260.3	ENSP00000272223.2		Q8TAX0
OSR1	ENST00000487581.1 link	n.3761G>A		non_coding_transcript_exon_variant	Exon 1 of 2	1

Frequencies

GnomAD3 genomes

AF:

0.108

AC:

16448

AN:

152136

Hom.:

1774

Cov.:

show subpopulations

Gnomad AFR

AF:

0.279

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.0598

Gnomad ASJ

AF:

0.0469

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0451

Gnomad FIN

AF:

0.0408

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0436

Gnomad OTH

AF:

0.0920

GnomAD2 exomes

AF:

0.0547

AC:

13742

AN:

251280

AF XY:

0.0523

show subpopulations

Gnomad AFR exome

AF:

0.280

Gnomad AMR exome

AF:

0.0304

Gnomad ASJ exome

AF:

0.0454

Gnomad EAS exome

AF:

0.000217

Gnomad FIN exome

AF:

0.0420

Gnomad NFE exome

AF:

0.0441

Gnomad OTH exome

AF:

0.0473

GnomAD4 exome

AF:

0.0449

AC:

65668

AN:

1461256

Hom.:

2676

Cov.:

AF XY:

0.0451

AC XY:

32776

AN XY:

726796

show subpopulations

African (AFR)

AF:

0.283

AC:

9462

AN:

33468

American (AMR)

AF:

0.0336

AC:

1503

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0462

AC:

1206

AN:

26130

East Asian (EAS)

AF:

0.000126

AC:

AN:

39698

South Asian (SAS)

AF:

0.0499

AC:

4306

AN:

86252

European-Finnish (FIN)

AF:

0.0437

AC:

2330

AN:

53370

Middle Eastern (MID)

AF:

0.0675

AC:

389

AN:

5762

European-Non Finnish (NFE)

AF:

0.0391

AC:

43408

AN:

1111486

Other (OTH)

AF:

0.0507

AC:

3059

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

3589

7178

10768

14357

17946

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.108

AC:

16507

AN:

152254

Hom.:

1791

Cov.:

AF XY:

0.107

AC XY:

7937

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.279

AC:

11593

AN:

41520

American (AMR)

AF:

0.0597

AC:

914

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.0469

AC:

163

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5186

South Asian (SAS)

AF:

0.0456

AC:

220

AN:

4828

European-Finnish (FIN)

AF:

0.0408

AC:

433

AN:

10604

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0436

AC:

2964

AN:

68016

Other (OTH)

AF:

0.0910

AC:

192

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

657

1314

1971

2628

3285

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0495

Hom.:

327

Bravo

AF:

0.115

Asia WGS

AF:

0.0330

AC:

116

AN:

3478

EpiCase

AF:

0.0452

EpiControl

AF:

0.0433

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 10, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 25164089, 21821672) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

0.58

(source)

DANN

Benign

0.91

PhyloP100

-0.35

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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2-19353152-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over