Genetic Variant OSR1:p.Leu218Leu (chr2-19353152-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -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

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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

GnomAD3 exomes

AF:

0.0547

AC:

13742

AN:

251280

Hom.:

902

AF XY:

0.0523

AC XY:

7106

AN XY:

135812

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 SAS exome

AF:

0.0479

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

Gnomad4 AFR exome

AF:

0.283

Gnomad4 AMR exome

AF:

0.0336

Gnomad4 ASJ exome

AF:

0.0462

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0499

Gnomad4 FIN exome

AF:

0.0437

Gnomad4 NFE exome

AF:

0.0391

Gnomad4 OTH exome

AF:

0.0507

GnomAD4 genome

AF:

0.108

AC:

16507

AN:

152254

Hom.:

1791

Cov.:

AF XY:

0.107

AC XY:

7937

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.279

Gnomad4 AMR

AF:

0.0597

Gnomad4 ASJ

AF:

0.0469

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0456

Gnomad4 FIN

AF:

0.0408

Gnomad4 NFE

AF:

0.0436

Gnomad4 OTH

AF:

0.0910

Alfa

AF:

0.0446

Hom.:

186

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

0.58

DANN

Benign

0.91

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over