chr22-30263948-C-G

Variant names:

• chr22-30263948-C-G
• rs971673051
• NM_020530.6:c.694G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020530.6(OSM):​c.694G>C​(p.Val232Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: OSM NM_020530.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06551349).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OSM	NM_020530.6	c.694G>C	p.Val232Leu	missense_variant	Exon 3 of 3	ENST00000215781.3	NP_065391.1
OSM	NM_001319108.2	c.631G>C	p.Val211Leu	missense_variant	Exon 3 of 3		NP_001306037.1
OSM	XM_047441387.1	c.631G>C	p.Val211Leu	missense_variant	Exon 3 of 3		XP_047297343.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OSM	ENST00000215781.3	c.694G>C	p.Val232Leu	missense_variant	Exon 3 of 3	1	NM_020530.6	ENSP00000215781.2
OSM	ENST00000403389.1	c.631G>C	p.Val211Leu	missense_variant	Exon 3 of 3	3		ENSP00000383893.1
OSM	ENST00000403463.1	c.*488G>C		downstream_gene_variant		3		ENSP00000384543.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.49
DANN	Benign	0.68
DEOGEN2	Benign	0.39	T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.34	T;T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.066	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L;.
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.014
Sift	Benign	0.34	T;T
Sift4G	Benign	0.38	T;T
Polyphen		0.077	B;.
Vest4		0.065
MutPred		0.11		Loss of methylation at R229 (P = 0.1274);.;
MVP		0.27
MPC		0.19
ClinPred		0.31	T
GERP RS		-4.8
Varity_R		0.058
gMVP		0.11

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

Other links and lift over

dbSNP: rs971673051; hg19: chr22-30659937;