NM_001127671.2:c.*5356A>G

Variant names:

• chr5-38476239-T-C
• rs7713531
• NM_001127671.2:c.*5356A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001127671.2(LIFR):​c.*5356A>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 0.0325 in 207,532 control chromosomes in the GnomAD database, including 473 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.041 (447 hom., cov: 33)
  • Exomes 𝑓: 0.0089 (26 hom.)
• Consequence: LIFR NM_001127671.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.44
• Publications: 1 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 5-38476239-T-C is Benign according to our data. Variant chr5-38476239-T-C is described in ClinVar as Benign. ClinVar VariationId is 353535.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.139 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.*5356A>G		3_prime_UTR	Exon 20 of 20	NP_001121143.1	P42702-1
	LIFR	NM_001364297.2		c.*5356A>G		3_prime_UTR	Exon 20 of 20	NP_001351226.1	P42702-1
	LIFR	NM_002310.6		c.*5356A>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.*5356A>G		3_prime_UTR	Exon 20 of 20	ENSP00000398368.2	P42702-1
	LIFR	ENST00000263409.8	TSL:1	c.*5356A>G		3_prime_UTR	Exon 20 of 20	ENSP00000263409.4	P42702-1
	LIFR	ENST00000929709.1		c.*5356A>G		3_prime_UTR	Exon 20 of 20	ENSP00000599768.1

Frequencies

GnomAD3 genomes AF: 0.0409 AC: 6223 AN: 152066 Hom.: 445 Cov.: 33

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.00769

Gnomad AMR AF: 0.0159

Gnomad ASJ AF: 0.00374

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000574

Gnomad OTH AF: 0.0292

GnomAD4 exome AF: 0.00894 AC: 495 AN: 55348 Hom.: 26 Cov.: 0 AF XY: 0.00832 AC XY: 214 AN XY: 25716

African (AFR) AF: 0.143 AC: 355 AN: 2486

American (AMR) AF: 0.0166 AC: 26 AN: 1568

Ashkenazi Jewish (ASJ) AF: 0.00341 AC: 12 AN: 3516

East Asian (EAS) AF: 0.00 AC: 0 AN: 8458

South Asian (SAS) AF: 0.00 AC: 0 AN: 462

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38

Middle Eastern (MID) AF: 0.00904 AC: 3 AN: 332

European-Non Finnish (NFE) AF: 0.000621 AC: 21 AN: 33842

Other (OTH) AF: 0.0168 AC: 78 AN: 4646

GnomAD4 genome AF: 0.0410 AC: 6246 AN: 152184 Hom.: 447 Cov.: 33 AF XY: 0.0387 AC XY: 2883 AN XY: 74414

African (AFR) AF: 0.142 AC: 5877 AN: 41506

American (AMR) AF: 0.0159 AC: 243 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00374 AC: 13 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.000574 AC: 39 AN: 67978

Other (OTH) AF: 0.0289 AC: 61 AN: 2112

Alfa AF: 0.0203 Hom.: 38

Bravo AF: 0.0474

Asia WGS AF: 0.00751 AC: 26 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Stuve-Wiedemann syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.12
DANN	Benign	0.52
PhyloP100		-1.4
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: rs7713531; hg19: chr5-38476341;