chr5-38475405-G-A

Variant names:

• chr5-38475405-G-A
• rs1046224
• NM_001127671.2:c.*6190C>T

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.*6190C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 196,310 control chromosomes in the GnomAD database, including 11,717 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (8208 hom., cov: 32)
  • Exomes 𝑓: 0.37 (3509 hom.)
• Consequence: LIFR NM_001127671.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.736
• Publications: 9 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: ClinGen, Orphanet
• 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=-0.73).
• BP6: Variant 5-38475405-G-A is Benign according to our data. Variant chr5-38475405-G-A is described in ClinVar as Benign. ClinVar VariationId is 353523.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.657 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.*6190C>T		3_prime_UTR	Exon 20 of 20	NP_001121143.1	P42702-1
	LIFR	NM_001364297.2		c.*6190C>T		3_prime_UTR	Exon 20 of 20	NP_001351226.1	P42702-1
	LIFR	NM_002310.6		c.*6190C>T		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.*6190C>T		3_prime_UTR	Exon 20 of 20	ENSP00000398368.2	P42702-1
	LIFR	ENST00000263409.8	TSL:1	c.*6190C>T		3_prime_UTR	Exon 20 of 20	ENSP00000263409.4	P42702-1
	LIFR	ENST00000929709.1		c.*6190C>T		3_prime_UTR	Exon 20 of 20	ENSP00000599768.1

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47843 AN: 151664 Hom.: 8203 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.676

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.327

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.323

GnomAD4 exome AF: 0.374 AC: 16647 AN: 44528 Hom.: 3509 Cov.: 0 AF XY: 0.370 AC XY: 7646 AN XY: 20654

African (AFR) AF: 0.197 AC: 381 AN: 1934

American (AMR) AF: 0.314 AC: 385 AN: 1226

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 644 AN: 2834

East Asian (EAS) AF: 0.656 AC: 4697 AN: 7158

South Asian (SAS) AF: 0.386 AC: 146 AN: 378

European-Finnish (FIN) AF: 0.333 AC: 149 AN: 448

Middle Eastern (MID) AF: 0.302 AC: 81 AN: 268

European-Non Finnish (NFE) AF: 0.336 AC: 8923 AN: 26592

Other (OTH) AF: 0.336 AC: 1241 AN: 3690

GnomAD4 genome AF: 0.315 AC: 47864 AN: 151782 Hom.: 8208 Cov.: 32 AF XY: 0.318 AC XY: 23613 AN XY: 74148

African (AFR) AF: 0.202 AC: 8359 AN: 41416

American (AMR) AF: 0.342 AC: 5224 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 830 AN: 3466

East Asian (EAS) AF: 0.676 AC: 3493 AN: 5166

South Asian (SAS) AF: 0.405 AC: 1946 AN: 4806

European-Finnish (FIN) AF: 0.319 AC: 3355 AN: 10518

Middle Eastern (MID) AF: 0.324 AC: 94 AN: 290

European-Non Finnish (NFE) AF: 0.348 AC: 23598 AN: 67846

Other (OTH) AF: 0.324 AC: 682 AN: 2104

Alfa AF: 0.337 Hom.: 9151

Bravo AF: 0.311

Asia WGS AF: 0.507 AC: 1754 AN: 3470

ClinVar

ClinVar submissions

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	-0.73
CADD	Benign	1.6
DANN	Benign	0.72
PhyloP100		0.74
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: rs1046224; hg19: chr5-38475507;