5-38474954-C-CT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001127671.2(LIFR):c.*6640_*6641insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0383 in 162,252 control chromosomes in the GnomAD database, including 426 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.040 (424 hom., cov: 32)
  • Exomes 𝑓: 0.0079 (2 hom.)
• Consequence: LIFR NM_001127671.2 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0760

Genes affected

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 -10 ACMG points.

• BP6: Variant 5-38474954-C-CT is Benign according to our data. Variant chr5-38474954-C-CT is described in ClinVar as [Likely_benign]. Clinvar id is 369474.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIFR	NM_001127671.2	c.*6640_*6641insA		3_prime_UTR_variant	20/20	ENST00000453190.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIFR	ENST00000453190.7	c.*6640_*6641insA		3_prime_UTR_variant	20/20	2	NM_001127671.2	P1
LIFR	ENST00000263409.8			downstream_gene_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.0402 AC: 6111 AN: 152084 Hom.: 422 Cov.: 32

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0157

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000544

Gnomad OTH AF: 0.0292

GnomAD4 exome AF: 0.00786 AC: 79 AN: 10050 Hom.: 2 Cov.: 0 AF XY: 0.00627 AC XY: 29 AN XY: 4628

Gnomad4 AFR exome AF: 0.141

Gnomad4 AMR exome AF: 0.0172

Gnomad4 ASJ exome AF: 0.00319

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000828

Gnomad4 OTH exome AF: 0.0175

GnomAD4 genome AF: 0.0403 AC: 6134 AN: 152202 Hom.: 424 Cov.: 32 AF XY: 0.0380 AC XY: 2831 AN XY: 74430

Gnomad4 AFR AF: 0.139

Gnomad4 AMR AF: 0.0157

Gnomad4 ASJ AF: 0.00375

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000544

Gnomad4 OTH AF: 0.0289

Alfa AF: 0.0337 Hom.: 34

Bravo AF: 0.0465

Asia WGS AF: 0.00779 AC: 27 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Stuve-Wiedemann syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs57386567; hg19: chr5-38475056;