rs6862038

Positions:

• chr5-38596366-A-G
• chr5-38596366-A-T

Variant summary

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

The XM_017009463.2(LIFR):​c.-142-983T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 151,930 control chromosomes in the GnomAD database, including 16,850 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 0.46 (16850 hom., cov: 32)
• Consequence: LIFR XM_017009463.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIFR	XM_017009463.2	c.-142-983T>C		intron_variant			XP_016864952.1
LIFR-AS1	NR_103553.1	n.2540+1297A>G		intron_variant
LIFR-AS1	NR_103554.1	n.2540+1297A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIFR-AS1	ENST00000500733.6	n.2540+1297A>G		intron_variant		1
LIFR-AS1	ENST00000500817.2	n.496+1297A>G		intron_variant		1
LIFR	ENST00000507786.1	n.306-983T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70396 AN: 151812 Hom.: 16824 Cov.: 32

Gnomad AFR AF: 0.573

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.585

Gnomad EAS AF: 0.565

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.415

Gnomad OTH AF: 0.466

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

GnomAD4 genome AF: 0.464 AC: 70475 AN: 151930 Hom.: 16850 Cov.: 32 AF XY: 0.463 AC XY: 34338 AN XY: 74226

Gnomad4 AFR AF: 0.574

Gnomad4 AMR AF: 0.372

Gnomad4 ASJ AF: 0.585

Gnomad4 EAS AF: 0.565

Gnomad4 SAS AF: 0.426

Gnomad4 FIN AF: 0.408

Gnomad4 NFE AF: 0.415

Gnomad4 OTH AF: 0.465

Alfa AF: 0.442 Hom.: 2955

Bravo AF: 0.467

Asia WGS AF: 0.510 AC: 1775 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.54
DANN	Benign	0.36

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6862038; hg19: chr5-38596468;