rs3822425

Variant names:

• chr5-38475925-T-C
• rs3822425
• NM_001127671.2:c.*5670A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001127671.2(LIFR):​c.*5670A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 192,484 control chromosomes in the GnomAD database, including 10,116 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (7738 hom., cov: 33)
  • Exomes 𝑓: 0.33 (2378 hom.)
• Consequence: LIFR NM_001127671.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.353
• Publications: 8 publications found

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]

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 5-38475925-T-C is Benign according to our data. Variant chr5-38475925-T-C is described in ClinVar as Benign. ClinVar VariationId is 353531.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001127671.2. 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	NM_001127671.2	MANE Select	c.*5670A>G		3_prime_UTR	Exon 20 of 20	NP_001121143.1	P42702-1
	LIFR	NM_001364297.2		c.*5670A>G		3_prime_UTR	Exon 20 of 20	NP_001351226.1	P42702-1
	LIFR	NM_002310.6		c.*5670A>G		3_prime_UTR	Exon 20 of 20	NP_002301.1	P42702-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIFR	ENST00000453190.7	TSL:2 MANE Select	c.*5670A>G		3_prime_UTR	Exon 20 of 20	ENSP00000398368.2	P42702-1
	LIFR	ENST00000263409.8	TSL:1	c.*5670A>G		3_prime_UTR	Exon 20 of 20	ENSP00000263409.4	P42702-1
	LIFR	ENST00000929709.1		c.*5670A>G		3_prime_UTR	Exon 20 of 20	ENSP00000599768.1

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47432 AN: 151926 Hom.: 7737 Cov.: 33

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.320

GnomAD4 exome AF: 0.330 AC: 13325 AN: 40438 Hom.: 2378 Cov.: 0 AF XY: 0.326 AC XY: 6101 AN XY: 18708

African (AFR) AF: 0.186 AC: 311 AN: 1674

American (AMR) AF: 0.337 AC: 360 AN: 1068

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 577 AN: 2562

East Asian (EAS) AF: 0.397 AC: 2771 AN: 6986

South Asian (SAS) AF: 0.377 AC: 125 AN: 332

European-Finnish (FIN) AF: 0.326 AC: 47 AN: 144

Middle Eastern (MID) AF: 0.299 AC: 73 AN: 244

European-Non Finnish (NFE) AF: 0.331 AC: 7970 AN: 24100

Other (OTH) AF: 0.328 AC: 1091 AN: 3328

GnomAD4 genome AF: 0.312 AC: 47445 AN: 152046 Hom.: 7738 Cov.: 33 AF XY: 0.314 AC XY: 23336 AN XY: 74318

African (AFR) AF: 0.209 AC: 8664 AN: 41514

American (AMR) AF: 0.381 AC: 5812 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 829 AN: 3464

East Asian (EAS) AF: 0.426 AC: 2203 AN: 5168

South Asian (SAS) AF: 0.388 AC: 1872 AN: 4820

European-Finnish (FIN) AF: 0.308 AC: 3250 AN: 10568

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.350 AC: 23762 AN: 67936

Other (OTH) AF: 0.320 AC: 673 AN: 2106

Alfa AF: 0.338 Hom.: 4157

Bravo AF: 0.311

Asia WGS AF: 0.397 AC: 1377 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Stuve-Wiedemann syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	10
DANN	Benign	0.76
PhyloP100		0.35
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs3822425; hg19: chr5-38476027; COSMIC: COSV105039490;