22-30262733-C-T

Variant names:

• chr22-30262733-C-T
• rs7289095
• NM_020530.6:c.*1150G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.649

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

Verdict is Benign. Variant got -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	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OSM	NM_020530.6	c.*1150G>A		downstream_gene_variant		ENST00000215781.3	NP_065391.1
OSM	NM_001319108.2	c.*1150G>A		downstream_gene_variant			NP_001306037.1
OSM	XM_047441387.1	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	c.*1150G>A		downstream_gene_variant		1	NM_020530.6	ENSP00000215781.2

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32522 AN: 151988 Hom.: 3794 Cov.: 33

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: 72 AN: 430 Hom.: 6 AF XY: 0.191 AC XY: 50 AN XY: 262

Gnomad4 EAS exome AF: 0.250

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.158

Gnomad4 NFE exome AF: 0.333

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.214 AC: 32559 AN: 152106 Hom.: 3804 Cov.: 33 AF XY: 0.212 AC XY: 15759 AN XY: 74346

Gnomad4 AFR AF: 0.310

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.249

Gnomad4 EAS AF: 0.202

Gnomad4 SAS AF: 0.205

Gnomad4 FIN AF: 0.170

Gnomad4 NFE AF: 0.180

Gnomad4 OTH AF: 0.217

Alfa AF: 0.180 Hom.: 4341

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
DANN	Benign	0.65

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7289095; hg19: chr22-30658722; COSMIC: COSV53161811;