Variant 5-38475925-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001127671.2(LIFR):c.*5670A>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 0.316 in 192,484 control chromosomes in the GnomAD database, including 10,116 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 7738 hom., cov: 33)

Exomes 𝑓: 0.33 ( 2378 hom. )

Consequence

LIFR
NM_001127671.2 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.353

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 5-38475925-T-C is Benign according to our data. Variant chr5-38475925-T-C is described in ClinVar as [Benign]. Clinvar id is 353531.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIFR	NM_001127671.2 link	c.*5670A>G		3_prime_UTR_variant	20/20	ENST00000453190.7	NP_001121143.1	P42702-1A8K1Z4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIFR	ENST00000453190 link	c.*5670A>G		3_prime_UTR_variant	20/20	2	NM_001127671.2	ENSP00000398368.2		P42702-1
LIFR	ENST00000263409 link	c.*5670A>G		3_prime_UTR_variant	20/20	1		ENSP00000263409.4		P42702-1

Frequencies

GnomAD3 genomes

AF:

0.312

AC:

47432

AN:

151926

Hom.:

7737

Cov.:

show subpopulations

Gnomad AFR

AF:

0.209

Gnomad AMI

AF:

0.310

Gnomad AMR

AF:

0.381

Gnomad ASJ

AF:

0.239

Gnomad EAS

AF:

0.426

Gnomad SAS

AF:

0.388

Gnomad FIN

AF:

0.308

Gnomad MID

AF:

0.332

Gnomad NFE

AF:

0.350

Gnomad OTH

AF:

0.320

GnomAD4 exome

AF:

0.330

AC:

13325

AN:

40438

Hom.:

2378

Cov.:

AF XY:

0.326

AC XY:

6101

AN XY:

18708

show subpopulations

Gnomad4 AFR exome

AF:

0.186

Gnomad4 AMR exome

AF:

0.337

Gnomad4 ASJ exome

AF:

0.225

Gnomad4 EAS exome

AF:

0.397

Gnomad4 SAS exome

AF:

0.377

Gnomad4 FIN exome

AF:

0.326

Gnomad4 NFE exome

AF:

0.331

Gnomad4 OTH exome

AF:

0.328

GnomAD4 genome

AF:

0.312

AC:

47445

AN:

152046

Hom.:

7738

Cov.:

AF XY:

0.314

AC XY:

23336

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.209

Gnomad4 AMR

AF:

0.381

Gnomad4 ASJ

AF:

0.239

Gnomad4 EAS

AF:

0.426

Gnomad4 SAS

AF:

0.388

Gnomad4 FIN

AF:

0.308

Gnomad4 NFE

AF:

0.350

Gnomad4 OTH

AF:

0.320

Alfa

AF:

0.341

Hom.:

3541

Bravo

AF:

0.311

Asia WGS

AF:

0.397

AC:

1377

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.76

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over