Genetic Variant NM_020530.6:c.*1150G>A (chr22-30262733-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020530.6(OSM):c.*1150G>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 152,536 control chromosomes in the GnomAD database, including 3,810 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 0.21 ( 3804 hom., cov: 33)

Exomes 𝑓: 0.17 ( 6 hom. )

Consequence

OSM
NM_020530.6 downstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.649

Publications

9 publications found

Variant links:

COSMIC-nc: COSV53161811

Genes affected

OSM (HGNC:8506): (oncostatin M) This gene encodes a member of the leukemia inhibitory factor/oncostatin-M (LIF/OSM) family of proteins. The encoded preproprotein is proteolytically processed to generate the mature protein. This protein is a secreted cytokine and growth regulator that inhibits the proliferation of a number of tumor cell lines. This protein also regulates the production of other cytokines, including interleukin 6, granulocyte-colony stimulating factor and granulocyte-macrophage colony stimulating factor in endothelial cells. This gene and the related gene, leukemia inhibitory factor, also present on chromosome 22, may have resulted from the duplication of a common ancestral gene. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Jan 2016]

OSM links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
OSM	NM_020530.6 link	c.*1150G>A	downstream_gene_variant	ENST00000215781.3	NP_065391.1	P13725
OSM	NM_001319108.2 link	c.*1150G>A	downstream_gene_variant		NP_001306037.1	P13725B5MCX1
OSM	XM_047441387.1 link	c.*1150G>A	downstream_gene_variant		XP_047297343.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OSM	ENST00000215781.3 link	c.*1150G>A		downstream_gene_variant		1	NM_020530.6	ENSP00000215781.2		P13725

Frequencies

GnomAD3 genomes

AF:

0.214

AC:

32522

AN:

151988

Hom.:

3794

Cov.:

show subpopulations

Gnomad AFR

AF:

0.310

Gnomad AMI

AF:

0.118

Gnomad AMR

AF:

0.139

Gnomad ASJ

AF:

0.249

Gnomad EAS

AF:

0.202

Gnomad SAS

AF:

0.206

Gnomad FIN

AF:

0.170

Gnomad MID

AF:

0.256

Gnomad NFE

AF:

0.180

Gnomad OTH

AF:

0.207

GnomAD4 exome

AF:

0.167

AC:

AN:

430

Hom.:

AF XY:

0.191

AC XY:

AN XY:

262

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.250

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.158

AC:

AN:

404

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.333

AC:

AN:

Other (OTH)

AF:

0.750

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.214

AC:

32559

AN:

152106

Hom.:

3804

Cov.:

AF XY:

0.212

AC XY:

15759

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.310

AC:

12857

AN:

41474

American (AMR)

AF:

0.140

AC:

2134

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.249

AC:

862

AN:

3466

East Asian (EAS)

AF:

0.202

AC:

1043

AN:

5162

South Asian (SAS)

AF:

0.205

AC:

990

AN:

4824

European-Finnish (FIN)

AF:

0.170

AC:

1794

AN:

10580

Middle Eastern (MID)

AF:

0.245

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.180

AC:

12242

AN:

67992

Other (OTH)

AF:

0.217

AC:

458

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1264

2528

3791

5055

6319

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

340

680

1020

1360

1700

<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:

0.189

Hom.:

10911

Bravo

AF:

0.216

Asia WGS

AF:

0.236

AC:

817

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

3.9

(source)

DANN

Benign

0.65

PhyloP100

-0.65

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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