Variant 5-38527126-T-G 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.397+29A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 1,553,396 control chromosomes in the GnomAD database, including 152,324 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 12466 hom., cov: 32)

Exomes 𝑓: 0.44 ( 139858 hom. )

Consequence

LIFR
NM_001127671.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.524

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:

LIFR (HGNC:):

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=-0.82).

BP6

Variant 5-38527126-T-G is Benign according to our data. Variant chr5-38527126-T-G is described in ClinVar as [Benign]. Clinvar id is 1185227.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIFR	NM_001127671.2 linkuse as main transcript	c.397+29A>C		intron_variant		ENST00000453190.7	NP_001121143.1	P42702-1A8K1Z4

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
LIFR	ENST00000453190.7 linkuse as main transcript	c.397+29A>C	intron_variant	2	NM_001127671.2	ENSP00000398368.2	P42702-1
LIFR	ENST00000263409.8 linkuse as main transcript	c.397+29A>C	intron_variant	1		ENSP00000263409.4	P42702-1
LIFR	ENST00000503088.1 linkuse as main transcript	n.560+29A>C	intron_variant	1
LIFR	ENST00000506990.5 linkuse as main transcript	c.*49A>C	downstream_gene_variant	3		ENSP00000426685.1	D6RF33

Frequencies

GnomAD3 genomes

AF:

0.386

AC:

58609

AN:

151992

Hom.:

12470

Cov.:

show subpopulations

Gnomad AFR

AF:

0.207

Gnomad AMI

AF:

0.443

Gnomad AMR

AF:

0.341

Gnomad ASJ

AF:

0.642

Gnomad EAS

AF:

0.541

Gnomad SAS

AF:

0.465

Gnomad FIN

AF:

0.490

Gnomad MID

AF:

0.528

Gnomad NFE

AF:

0.455

Gnomad OTH

AF:

0.432

GnomAD3 exomes

AF:

0.429

AC:

90598

AN:

211356

Hom.:

20766

AF XY:

0.441

AC XY:

50073

AN XY:

113486

show subpopulations

Gnomad AFR exome

AF:

0.199

Gnomad AMR exome

AF:

0.250

Gnomad ASJ exome

AF:

0.638

Gnomad EAS exome

AF:

0.545

Gnomad SAS exome

AF:

0.471

Gnomad FIN exome

AF:

0.480

Gnomad NFE exome

AF:

0.457

Gnomad OTH exome

AF:

0.459

GnomAD4 exome

AF:

0.440

AC:

616782

AN:

1401286

Hom.:

139858

Cov.:

AF XY:

0.444

AC XY:

309546

AN XY:

696510

show subpopulations

Gnomad4 AFR exome

AF:

0.198

Gnomad4 AMR exome

AF:

0.262

Gnomad4 ASJ exome

AF:

0.635

Gnomad4 EAS exome

AF:

0.552

Gnomad4 SAS exome

AF:

0.471

Gnomad4 FIN exome

AF:

0.476

Gnomad4 NFE exome

AF:

0.440

Gnomad4 OTH exome

AF:

0.450

GnomAD4 genome

AF:

0.385

AC:

58606

AN:

152110

Hom.:

12466

Cov.:

AF XY:

0.390

AC XY:

28968

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.206

Gnomad4 AMR

AF:

0.341

Gnomad4 ASJ

AF:

0.642

Gnomad4 EAS

AF:

0.540

Gnomad4 SAS

AF:

0.464

Gnomad4 FIN

AF:

0.490

Gnomad4 NFE

AF:

0.455

Gnomad4 OTH

AF:

0.428

Alfa

AF:

0.439

Hom.:

8979

Bravo

AF:

0.366

Asia WGS

AF:

0.479

AC:

1668

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 20, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Stuve-Wiedemann syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.9

DANN

Benign

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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