5-38476239-T-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001127671.2(LIFR):​c.*5356A>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 0.0000181 in 55,356 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: LIFR NM_001127671.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

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>T		3_prime_UTR	Exon 20 of 20	NP_001121143.1	P42702-1
	LIFR	NM_001364297.2		c.*5356A>T		3_prime_UTR	Exon 20 of 20	NP_001351226.1	P42702-1
	LIFR	NM_002310.6		c.*5356A>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.*5356A>T		3_prime_UTR	Exon 20 of 20	ENSP00000398368.2	P42702-1
	LIFR	ENST00000263409.8	TSL:1	c.*5356A>T		3_prime_UTR	Exon 20 of 20	ENSP00000263409.4	P42702-1
	LIFR	ENST00000929709.1		c.*5356A>T		3_prime_UTR	Exon 20 of 20	ENSP00000599768.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000181 AC: 1 AN: 55356 Hom.: 0 Cov.: 0 AF XY: 0.0000389 AC XY: 1 AN XY: 25722

African (AFR) AF: 0.00 AC: 0 AN: 2488

American (AMR) AF: 0.00 AC: 0 AN: 1572

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 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: 0.00 AC: 0 AN: 332

European-Non Finnish (NFE) AF: 0.0000295 AC: 1 AN: 33842

Other (OTH) AF: 0.00 AC: 0 AN: 4648

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.085
DANN	Benign	0.63
PhyloP100		-1.4

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;