5-38542187-A-G

Variant names:

• chr5-38542187-A-G
• rs10512686
• NM_001127671.2:c.-19-11521T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001127671.2(LIFR):​c.-19-11521T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 152,114 control chromosomes in the GnomAD database, including 7,146 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.30 (7146 hom., cov: 32)
• Consequence: LIFR NM_001127671.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.775
• Publications: 3 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: ClinGen, Orphanet
• Stüve-Wiedemann syndrome 1

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIFR	NM_001127671.2	c.-19-11521T>C		intron_variant	Intron 1 of 19	ENST00000453190.7	NP_001121143.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIFR	ENST00000453190.7	c.-19-11521T>C		intron_variant	Intron 1 of 19	2	NM_001127671.2	ENSP00000398368.2

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45626 AN: 151994 Hom.: 7147 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.310

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.300 AC: 45637 AN: 152114 Hom.: 7146 Cov.: 32 AF XY: 0.302 AC XY: 22436 AN XY: 74322

African (AFR) AF: 0.202 AC: 8381 AN: 41516

American (AMR) AF: 0.335 AC: 5123 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 821 AN: 3468

East Asian (EAS) AF: 0.414 AC: 2134 AN: 5160

South Asian (SAS) AF: 0.393 AC: 1891 AN: 4816

European-Finnish (FIN) AF: 0.298 AC: 3145 AN: 10560

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.340 AC: 23111 AN: 67988

Other (OTH) AF: 0.310 AC: 655 AN: 2112

Alfa AF: 0.308 Hom.: 3838

Bravo AF: 0.295

Asia WGS AF: 0.384 AC: 1334 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.16
DANN	Benign	0.67
PhyloP100		-0.78
Mutation Taster		=100/0	polymorphism (auto)

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: rs10512686; hg19: chr5-38542289;