NM_002309.5:c.451G>C

Variant names:

• chr22-30243809-C-G
• rs753939297
• NM_002309.5:c.451G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002309.5(LIF):​c.451G>C​(p.Val151Leu) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V151M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LIF NM_002309.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.82
• Publications: 5 publications found

Genes affected

LIF (HGNC:6596): (LIF interleukin 6 family cytokine) The protein encoded by this gene is a pleiotropic cytokine with roles in several different systems. It is involved in the induction of hematopoietic differentiation in normal and myeloid leukemia cells, induction of neuronal cell differentiation, regulator of mesenchymal to epithelial conversion during kidney development, and may also have a role in immune tolerance at the maternal-fetal interface. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Mar 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3910944).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002309.5. 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
	LIF	NM_002309.5	MANE Select	c.451G>C	p.Val151Leu	missense	Exon 3 of 3	NP_002300.1	P15018-1
	LIF	NM_001257135.2		c.*5G>C		3_prime_UTR	Exon 2 of 2	NP_001244064.1	P15018-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIF	ENST00000249075.4	TSL:1 MANE Select	c.451G>C	p.Val151Leu	missense	Exon 3 of 3	ENSP00000249075.3	P15018-1
	LIF	ENST00000403987.3	TSL:1	c.*5G>C		3_prime_UTR	Exon 2 of 2	ENSP00000384450.3	P15018-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Benign	-0.087	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.32	T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.066	D
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-0.56	T
MutationAssessor	Benign	0.92	L
PhyloP100		1.8
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.16	N
REVEL	Uncertain	0.30
Sift	Benign	0.52	T
Sift4G	Benign	1.0	T
Polyphen		0.99	D
Vest4		0.14
MutPred		0.75		Loss of MoRF binding (P = 0.1846)
MVP		0.70
MPC		0.34
ClinPred		0.49	T
GERP RS		3.9
Varity_R		0.18
gMVP		0.40
Mutation Taster		=83/17	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: rs753939297; hg19: chr22-30639798;