5-38595604-C-G

Variant names:

• chr5-38595604-C-G
• rs2071237
• ENST00000500733.6:n.2540+535C>G

Variant summary

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

The XM_017009463.2(LIFR):​c.-142-221G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 151,942 control chromosomes in the GnomAD database, including 9,348 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 0.33 (9348 hom., cov: 32)
• Consequence: LIFR XM_017009463.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.537

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIFR	XM_017009463.2	c.-142-221G>C		intron_variant	Intron 2 of 21		XP_016864952.1
LIFR-AS1	NR_103553.1	n.2540+535C>G		intron_variant	Intron 2 of 2
LIFR-AS1	NR_103554.1	n.2540+535C>G		intron_variant	Intron 2 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIFR-AS1	ENST00000500733.6	n.2540+535C>G		intron_variant	Intron 2 of 2	1
LIFR-AS1	ENST00000500817.2	n.496+535C>G		intron_variant	Intron 2 of 8	1
LIFR	ENST00000507786.1	n.306-221G>C		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50627 AN: 151826 Hom.: 9353 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.580

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.409

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.367

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

GnomAD4 genome AF: 0.333 AC: 50616 AN: 151942 Hom.: 9348 Cov.: 32 AF XY: 0.335 AC XY: 24865 AN XY: 74270

Gnomad4 AFR AF: 0.174

Gnomad4 AMR AF: 0.277

Gnomad4 ASJ AF: 0.580

Gnomad4 EAS AF: 0.321

Gnomad4 SAS AF: 0.387

Gnomad4 FIN AF: 0.409

Gnomad4 NFE AF: 0.412

Gnomad4 OTH AF: 0.363

Alfa AF: 0.243 Hom.: 658

Bravo AF: 0.316

Asia WGS AF: 0.347 AC: 1211 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	9.1
DANN	Benign	0.68

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2071237; hg19: chr5-38595706;