5-38527126-T-G

Variant names:

• chr5-38527126-T-G
• rs2289779
• NM_001127671.2:c.397+29A>C

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.397+29A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 1,553,396 control chromosomes in the GnomAD database, including 152,324 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (12466 hom., cov: 32)
  • Exomes 𝑓: 0.44 (139858 hom.)
• Consequence: LIFR NM_001127671.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.524
• Publications: 14 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=-0.82).
• BP6: Variant 5-38527126-T-G is Benign according to our data. Variant chr5-38527126-T-G is described in ClinVar as Benign. ClinVar VariationId is 1185227.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.524 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIFR	NM_001127671.2	MANE Select	c.397+29A>C		intron	N/A	NP_001121143.1
	LIFR	NM_001364297.2		c.397+29A>C		intron	N/A	NP_001351226.1
	LIFR	NM_002310.6		c.397+29A>C		intron	N/A	NP_002301.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIFR	ENST00000453190.7	TSL:2 MANE Select	c.397+29A>C		intron	N/A	ENSP00000398368.2
	LIFR	ENST00000263409.8	TSL:1	c.397+29A>C		intron	N/A	ENSP00000263409.4
	LIFR	ENST00000503088.1	TSL:1	n.560+29A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58609 AN: 151992 Hom.: 12470 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.541

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.432

GnomAD2 exomes AF: 0.429 AC: 90598 AN: 211356 AF XY: 0.441

Gnomad AFR exome AF: 0.199

Gnomad AMR exome AF: 0.250

Gnomad ASJ exome AF: 0.638

Gnomad EAS exome AF: 0.545

Gnomad FIN exome AF: 0.480

Gnomad NFE exome AF: 0.457

Gnomad OTH exome AF: 0.459

GnomAD4 exome AF: 0.440 AC: 616782 AN: 1401286 Hom.: 139858 Cov.: 27 AF XY: 0.444 AC XY: 309546 AN XY: 696510

African (AFR) AF: 0.198 AC: 6395 AN: 32280

American (AMR) AF: 0.262 AC: 10571 AN: 40300

Ashkenazi Jewish (ASJ) AF: 0.635 AC: 16020 AN: 25232

East Asian (EAS) AF: 0.552 AC: 21344 AN: 38648

South Asian (SAS) AF: 0.471 AC: 38539 AN: 81784

European-Finnish (FIN) AF: 0.476 AC: 24603 AN: 51634

Middle Eastern (MID) AF: 0.549 AC: 3051 AN: 5556

European-Non Finnish (NFE) AF: 0.440 AC: 470161 AN: 1067904

Other (OTH) AF: 0.450 AC: 26098 AN: 57948

GnomAD4 genome AF: 0.385 AC: 58606 AN: 152110 Hom.: 12466 Cov.: 32 AF XY: 0.390 AC XY: 28968 AN XY: 74366

African (AFR) AF: 0.206 AC: 8571 AN: 41510

American (AMR) AF: 0.341 AC: 5207 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.642 AC: 2226 AN: 3468

East Asian (EAS) AF: 0.540 AC: 2792 AN: 5166

South Asian (SAS) AF: 0.464 AC: 2238 AN: 4824

European-Finnish (FIN) AF: 0.490 AC: 5180 AN: 10576

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.455 AC: 30929 AN: 67964

Other (OTH) AF: 0.428 AC: 903 AN: 2110

Alfa AF: 0.438 Hom.: 11524

Bravo AF: 0.366

Asia WGS AF: 0.479 AC: 1668 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Aug 20, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Stuve-Wiedemann syndrome Benign:1

Jul 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.9
DANN	Benign	0.64
PhyloP100		-0.52
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs2289779; hg19: chr5-38527228; COSMIC: COSV54686598; COSMIC: COSV54686598;