NM_001127671.2:c.452C>G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP6BS2

The NM_001127671.2(LIFR):c.452C>G(p.Ser151Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000408 in 1,613,098 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00044 ( 2 hom. )

Consequence

LIFR
NM_001127671.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:3B:1

Conservation

PhyloP100: 2.09

Publications

4 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: Likely_benign. The variant received -5 ACMG points.

BP6

Variant 5-38523528-G-C is Benign according to our data. Variant chr5-38523528-G-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 501917.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

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	UniProt
LIFR	NM_001127671.2	MANE Select	c.452C>G	p.Ser151Cys	missense	Exon 5 of 20	NP_001121143.1	P42702-1
LIFR	NM_001364297.2		c.452C>G	p.Ser151Cys	missense	Exon 5 of 20	NP_001351226.1	P42702-1
LIFR	NM_002310.6		c.452C>G	p.Ser151Cys	missense	Exon 5 of 20	NP_002301.1	P42702-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LIFR	ENST00000453190.7	TSL:2 MANE Select	c.452C>G	p.Ser151Cys	missense	Exon 5 of 20	ENSP00000398368.2	P42702-1
LIFR	ENST00000263409.8	TSL:1	c.452C>G	p.Ser151Cys	missense	Exon 5 of 20	ENSP00000263409.4	P42702-1
LIFR	ENST00000503088.1	TSL:1	n.615C>G		non_coding_transcript_exon	Exon 5 of 15

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000956

AC:

AN:

251086

AF XY:

0.0000810

show subpopulations

Gnomad AFR exome

AF:

0.0000619

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:

0.000203

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000435

AC:

636

AN:

1460912

Hom.:

Cov.:

AF XY:

0.000422

AC XY:

307

AN XY:

726830

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33450

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26118

East Asian (EAS)

AF:

0.00

AC:

AN:

39628

South Asian (SAS)

AF:

0.00

AC:

AN:

86228

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.000568

AC:

631

AN:

1111220

Other (OTH)

AF:

0.0000828

AC:

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

116

145

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

120

150

<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

AF:

0.000145

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.0000965

AC:

AN:

41454

American (AMR)

AF:

0.0000655

AC:

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5202

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000235

AC:

AN:

68038

Other (OTH)

AF:

0.000478

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000134

Hom.:

Bravo

AF:

0.000121

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000494

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000415

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Stüve-Wiedemann syndrome 1 (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.52

Eigen

Benign

0.19

Eigen_PC

Benign

0.036

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.81

M_CAP

Benign

0.040

MetaRNN

Uncertain

0.67

MetaSVM

Benign

-0.61

MutationAssessor

Uncertain

2.4

PhyloP100

2.1

PrimateAI

Benign

0.44

PROVEAN

Benign

-2.3

REVEL

Uncertain

0.30

Sift

Uncertain

0.012

Sift4G

Uncertain

0.027

Polyphen

1.0

Vest4

0.63

MVP

0.79

MPC

0.36

ClinPred

0.15

GERP RS

4.5

Varity_R

0.29

gMVP

0.33

Mutation Taster

=90/10

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over