rs2071236

Positions:

• chr5-38595658-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_017009463.2(LIFR):​c.-142-275C>T 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 XM_017009463.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.373

Genes affected

LIFR-AS1 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -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	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIFR	XM_017009463.2	c.-142-275C>T		intron_variant			XP_016864952.1
LIFR-AS1	NR_103553.1	n.2540+589G>A		intron_variant
LIFR-AS1	NR_103554.1	n.2540+589G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIFR-AS1	ENST00000500733.6	n.2540+589G>A		intron_variant		1
LIFR-AS1	ENST00000500817.2	n.496+589G>A		intron_variant		1
LIFR	ENST00000507786.1	n.306-275C>T		intron_variant		3

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

Gnomad4 AFR AF: 0.205

Gnomad4 AMR AF: 0.397

Gnomad4 ASJ AF: 0.318

Gnomad4 EAS AF: 0.394

Gnomad4 SAS AF: 0.427

Gnomad4 FIN AF: 0.406

Gnomad4 NFE AF: 0.382

Gnomad4 OTH AF: 0.354

Alfa AF: 0.369 Hom.: 6242

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
DANN	Benign	0.38

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2071236; hg19: chr5-38595760;