dbSNP rs2071236: LIFR-AS1:n.2540+589G>A (chr5-38595658-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000500733.6(LIFR-AS1):n.2540+589G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 151,190 control chromosomes in the GnomAD database, including 9,035 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 0.34 ( 9035 hom., cov: 29)

Consequence

LIFR-AS1
ENST00000500733.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.373

Publications

7 publications found

Variant links:

Genes affected

LIFR-AS1 (HGNC:43600): (LIFR antisense RNA 1)

LIFR-AS1 links:

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)

LIFR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
LIFR-AS1	NR_103553.1 link	n.2540+589G>A	intron_variant	Intron 2 of 2
LIFR-AS1	NR_103554.1 link	n.2540+589G>A	intron_variant	Intron 2 of 8
LIFR	XM_017009463.2 link	c.-142-275C>T	intron_variant	Intron 2 of 21	XP_016864952.1	P42702-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
LIFR-AS1	ENST00000500733.6 link	n.2540+589G>A	intron_variant	Intron 2 of 2	1
LIFR-AS1	ENST00000500817.2 link	n.496+589G>A	intron_variant	Intron 2 of 8	1
LIFR	ENST00000507786.1 link	n.306-275C>T	intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.336

AC:

50833

AN:

151078

Hom.:

9038

Cov.:

show subpopulations

Gnomad AFR

AF:

0.205

Gnomad AMI

AF:

0.298

Gnomad AMR

AF:

0.397

Gnomad ASJ

AF:

0.318

Gnomad EAS

AF:

0.394

Gnomad SAS

AF:

0.427

Gnomad FIN

AF:

0.406

Gnomad MID

AF:

0.430

Gnomad NFE

AF:

0.382

Gnomad OTH

AF:

0.354

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

GnomAD4 genome

AF:

0.336

AC:

50844

AN:

151190

Hom.:

9035

Cov.:

AF XY:

0.341

AC XY:

25165

AN XY:

73798

show subpopulations

African (AFR)

AF:

0.205

AC:

8441

AN:

41246

American (AMR)

AF:

0.397

AC:

6035

AN:

15188

Ashkenazi Jewish (ASJ)

AF:

0.318

AC:

1102

AN:

3464

East Asian (EAS)

AF:

0.394

AC:

2011

AN:

5098

South Asian (SAS)

AF:

0.427

AC:

2038

AN:

4772

European-Finnish (FIN)

AF:

0.406

AC:

4189

AN:

10324

Middle Eastern (MID)

AF:

0.431

AC:

125

AN:

290

European-Non Finnish (NFE)

AF:

0.382

AC:

25891

AN:

67808

Other (OTH)

AF:

0.354

AC:

743

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1627

3254

4881

6508

8135

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

518

1036

1554

2072

2590

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.370

Hom.:

6788

Bravo

AF:

0.325

Asia WGS

AF:

0.390

AC:

1354

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

6.0

(source)

DANN

Benign

0.38

PhyloP100

0.37

PromoterAI

-0.023

Neutral

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over