5-38523477-G-A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001127671.2(LIFR):c.503C>T(p.Ser168Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,372 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

LIFR
NM_001127671.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.18

Publications

0 publications found

Variant links:

Genes affected

LIFR (HGNC:6597): (LIF receptor subunit alpha) This gene encodes a protein that belongs to the type I cytokine receptor family. This protein combines with a high-affinity converter subunit, gp130, to form a receptor complex that mediates the action of the leukemia inhibitory factor, a polyfunctional cytokine that is involved in cellular differentiation, proliferation and survival in the adult and the embryo. Mutations in this gene cause Schwartz-Jampel syndrome type 2, a disease belonging to the group of the bent-bone dysplasias. A translocation that involves the promoter of this gene, t(5;8)(p13;q12) with the pleiomorphic adenoma gene 1, is associated with salivary gland pleiomorphic adenoma, a common type of benign epithelial tumor of the salivary gland. Multiple splice variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jun 2018]

LIFR Gene-Disease associations (from GenCC):

Stüve-Wiedemann syndrome
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
Stüve-Wiedemann syndrome 1
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

LIFR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07968184).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001127671.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
LIFR	NM_001127671.2	MANE Select	c.503C>T	p.Ser168Leu	missense	Exon 5 of 20	NP_001121143.1
LIFR	NM_001364297.2		c.503C>T	p.Ser168Leu	missense	Exon 5 of 20	NP_001351226.1
LIFR	NM_002310.6		c.503C>T	p.Ser168Leu	missense	Exon 5 of 20	NP_002301.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
LIFR	ENST00000453190.7	TSL:2 MANE Select	c.503C>T	p.Ser168Leu	missense	Exon 5 of 20	ENSP00000398368.2
LIFR	ENST00000263409.8	TSL:1	c.503C>T	p.Ser168Leu	missense	Exon 5 of 20	ENSP00000263409.4
LIFR	ENST00000503088.1	TSL:1	n.666C>T		non_coding_transcript_exon	Exon 5 of 15

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000797

AC:

AN:

250796

AF XY:

0.0000148

show subpopulations

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:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461372

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726988

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33454

American (AMR)

AF:

0.00

AC:

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39632

South Asian (SAS)

AF:

0.00

AC:

AN:

86184

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1111732

Other (OTH)

AF:

0.00

AC:

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

Cov.:

Alfa

AF:

0.0000116

Hom.:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Benign

0.28

DEOGEN2

Benign

0.22

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.074

LIST_S2

Benign

0.70

M_CAP

Benign

0.0042

MetaRNN

Benign

0.080

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.1

PhyloP100

1.2

PrimateAI

Benign

0.34

PROVEAN

Benign

0.98

REVEL

Benign

0.011

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.061

Vest4

0.20

MutPred

0.44

Gain of catalytic residue at S168 (P = 0.0107)

MVP

0.33

MPC

0.076

ClinPred

0.030

GERP RS

2.8

Varity_R

0.12

gMVP

0.22

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over