rs2071236

Variant names:

• chr5-38595658-G-A
• rs2071236
• ENST00000500733.6:n.2540+589G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.373
• Publications: 7 publications found

Genes affected

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

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: Orphanet, ClinGen
• Stüve-Wiedemann syndrome 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000500733.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIFR-AS1	NR_103553.1		n.2540+589G>A		intron	N/A
	LIFR-AS1	NR_103554.1		n.2540+589G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIFR-AS1	ENST00000500733.6	TSL:1	n.2540+589G>A		intron	N/A
	LIFR-AS1	ENST00000500817.2	TSL:1	n.496+589G>A		intron	N/A
	LIFR	ENST00000507786.1	TSL:3	n.306-275C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.336 AC: 50833 AN: 151078 Hom.: 9038 Cov.: 29

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.: 29 AF XY: 0.341 AC XY: 25165 AN XY: 73798

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.0
DANN	Benign	0.38
PhyloP100		0.37
PromoterAI		-0.023	Neutral

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2071236;

hg19: chr5-38595760;