rs200525725

Variant names:

• chr22-30264163-G-A
• rs200525725
• NM_020530.6:c.479C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_020530.6(OSM):​c.479C>T​(p.Ser160Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,613,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S160A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: OSM NM_020530.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.459
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.16229153).
• BS2: High AC in GnomAdExome4 at 27 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020530.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSM	NM_020530.6	MANE Select	c.479C>T	p.Ser160Leu	missense	Exon 3 of 3	NP_065391.1	P13725
	OSM	NM_001319108.2		c.416C>T	p.Ser139Leu	missense	Exon 3 of 3	NP_001306037.1	B5MCX1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSM	ENST00000215781.3	TSL:1 MANE Select	c.479C>T	p.Ser160Leu	missense	Exon 3 of 3	ENSP00000215781.2	P13725
	OSM	ENST00000403389.1	TSL:3	c.416C>T	p.Ser139Leu	missense	Exon 3 of 3	ENSP00000383893.1	B5MCX1
	OSM	ENST00000403463.1	TSL:3	c.*273C>T		3_prime_UTR	Exon 2 of 2	ENSP00000384543.1	B5MC70

Frequencies

GnomAD3 genomes AF: 0.0000328 AC: 5 AN: 152252 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000723

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250734 AF XY: 0.00000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000185 AC: 27 AN: 1461442 Hom.: 0 Cov.: 31 AF XY: 0.0000234 AC XY: 17 AN XY: 727030

African (AFR) AF: 0.000597 AC: 20 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53020

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111984

Other (OTH) AF: 0.0000662 AC: 4 AN: 60388

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152370 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74510

African (AFR) AF: 0.0000721 AC: 3 AN: 41588

American (AMR) AF: 0.00 AC: 0 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68034

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.031	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.79	D
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.088	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L
PhyloP100		0.46
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.14
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.030	D
Polyphen		1.0	D
Vest4		0.12
MVP		0.55
MPC		0.61
ClinPred		0.54	D
GERP RS		1.8
Varity_R		0.11
gMVP		0.21
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs200525725; hg19: chr22-30660152;