Variant 5-38594967-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_002310.6(LIFR):c.-20+294A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00427 in 193,638 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0048 ( 14 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 2 hom. )

Consequence

LIFR
NM_002310.6 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.429

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-AS1 (HGNC:):

LIFR-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 5-38594967-T-A is Benign according to our data. Variant chr5-38594967-T-A is described in ClinVar as [Benign]. Clinvar id is 439860.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0048 (731/152254) while in subpopulation AMR AF= 0.0412 (630/15290). AF 95% confidence interval is 0.0385. There are 14 homozygotes in gnomad4. There are 410 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	Protein	UniProt
LIFR	XM_047417172.1 linkuse as main transcript	c.-104A>T	5_prime_UTR_variant	2/21	XP_047273128.1
LIFR	NM_002310.6 linkuse as main transcript	c.-20+294A>T	intron_variant		NP_002301.1	P42702-1
LIFR	XM_017009463.2 linkuse as main transcript	c.-20+294A>T	intron_variant		XP_016864952.1	P42702-1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	Protein	UniProt
LIFR	ENST00000263409.8 linkuse as main transcript	c.-20+294A>T	intron_variant		1	ENSP00000263409.4	P42702-1
LIFR-AS1	ENST00000500733.6 linkuse as main transcript	n.2438T>A	non_coding_transcript_exon_variant	2/3	1
LIFR-AS1	ENST00000500817.2 linkuse as main transcript	n.394T>A	non_coding_transcript_exon_variant	2/9	1

Frequencies

GnomAD3 genomes

AF:

0.00479

AC:

728

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00138

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0411

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00669

GnomAD4 exome

AF:

0.00232

AC:

AN:

41384

Hom.:

Cov.:

AF XY:

0.00198

AC XY:

AN XY:

19160

show subpopulations

Gnomad4 AFR exome

AF:

0.00182

Gnomad4 AMR exome

AF:

0.0384

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00349

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000283

Gnomad4 OTH exome

AF:

0.00579

GnomAD4 genome

AF:

0.00480

AC:

731

AN:

152254

Hom.:

Cov.:

AF XY:

0.00551

AC XY:

410

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.00137

Gnomad4 AMR

AF:

0.0412

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00339

Hom.:

Bravo

AF:

0.00814

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Stuve-Wiedemann syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Aug 22, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.0

DANN

Benign

0.68

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