5-38475405-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001127671.2(LIFR):c.*6190C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 196,310 control chromosomes in the GnomAD database, including 11,717 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.32 (8208 hom., cov: 32)
  • Exomes 𝑓: 0.37 (3509 hom.)
• Consequence: LIFR NM_001127671.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.736

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 5-38475405-G-A is Benign according to our data. Variant chr5-38475405-G-A is described in ClinVar as [Benign]. Clinvar id is 353523.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIFR	NM_001127671.2	c.*6190C>T		3_prime_UTR_variant	20/20	ENST00000453190.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIFR	ENST00000453190.7	c.*6190C>T		3_prime_UTR_variant	20/20	2	NM_001127671.2	P1
LIFR	ENST00000263409.8	c.*6190C>T		3_prime_UTR_variant	20/20	1		P1

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47843 AN: 151664 Hom.: 8203 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.676

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.327

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.323

GnomAD4 exome AF: 0.374 AC: 16647 AN: 44528 Hom.: 3509 Cov.: 0 AF XY: 0.370 AC XY: 7646 AN XY: 20654

Gnomad4 AFR exome AF: 0.197

Gnomad4 AMR exome AF: 0.314

Gnomad4 ASJ exome AF: 0.227

Gnomad4 EAS exome AF: 0.656

Gnomad4 SAS exome AF: 0.386

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.336

Gnomad4 OTH exome AF: 0.336

GnomAD4 genome AF: 0.315 AC: 47864 AN: 151782 Hom.: 8208 Cov.: 32 AF XY: 0.318 AC XY: 23613 AN XY: 74148

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.342

Gnomad4 ASJ AF: 0.239

Gnomad4 EAS AF: 0.676

Gnomad4 SAS AF: 0.405

Gnomad4 FIN AF: 0.319

Gnomad4 NFE AF: 0.348

Gnomad4 OTH AF: 0.324

Alfa AF: 0.337 Hom.: 7927

Bravo AF: 0.311

Asia WGS AF: 0.507 AC: 1754 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Stuve-Wiedemann syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	1.6
Dann	Benign	0.72

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

LitVar

Other links and lift over

dbSNP: rs1046224; hg19: chr5-38475507;