rs560182899

Variant names:

• chr5-38475347-G-C
• rs560182899
• NM_001127671.2:c.*6248C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001127671.2(LIFR):​c.*6248C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000102 in 195,288 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000093 (0 hom.)
• Consequence: LIFR NM_001127671.2 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.143
• Publications: 0 publications found

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: Orphanet, ClinGen
• Stüve-Wiedemann syndrome 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIFR	NM_001127671.2	MANE Select	c.*6248C>G		3_prime_UTR	Exon 20 of 20	NP_001121143.1	P42702-1
	LIFR	NM_001364297.2		c.*6248C>G		3_prime_UTR	Exon 20 of 20	NP_001351226.1	P42702-1
	LIFR	NM_002310.6		c.*6248C>G		3_prime_UTR	Exon 20 of 20	NP_002301.1	P42702-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIFR	ENST00000453190.7	TSL:2 MANE Select	c.*6248C>G		3_prime_UTR	Exon 20 of 20	ENSP00000398368.2	P42702-1
	LIFR	ENST00000263409.8	TSL:1	c.*6248C>G		3_prime_UTR	Exon 20 of 20	ENSP00000263409.4	P42702-1
	LIFR	ENST00000929709.1		c.*6248C>G		3_prime_UTR	Exon 20 of 20	ENSP00000599768.1

Frequencies

GnomAD3 genomes AF: 0.000105 AC: 16 AN: 152004 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.000221

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000927 AC: 4 AN: 43164 Hom.: 0 Cov.: 0 AF XY: 0.0000497 AC XY: 1 AN XY: 20108

African (AFR) AF: 0.000543 AC: 1 AN: 1842

American (AMR) AF: 0.00 AC: 0 AN: 1202

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2694

East Asian (EAS) AF: 0.00 AC: 0 AN: 7034

South Asian (SAS) AF: 0.00 AC: 0 AN: 376

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 432

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 260

European-Non Finnish (NFE) AF: 0.000116 AC: 3 AN: 25810

Other (OTH) AF: 0.00 AC: 0 AN: 3514

GnomAD4 genome AF: 0.000105 AC: 16 AN: 152124 Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6 AN XY: 74364

African (AFR) AF: 0.0000241 AC: 1 AN: 41518

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 67964

Other (OTH) AF: 0.00 AC: 0 AN: 2106

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.0000718

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Stuve-Wiedemann syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.95
DANN	Benign	0.45
PhyloP100		0.14

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: rs560182899; hg19: chr5-38475449;