dbSNP rs115572283: LIFR:c.*6316C>T (chr5-38475279-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001127671.2(LIFR):c.*6316C>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 0.0101 in 193,928 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.012 ( 36 hom., cov: 33)

Exomes 𝑓: 0.0018 ( 1 hom. )

Consequence

LIFR
NM_001127671.2 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0340

Publications

0 publications found

Variant links:

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)

LIFR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 5-38475279-G-A is Benign according to our data. Variant chr5-38475279-G-A is described in ClinVar as Benign. ClinVar VariationId is 353522.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0123 (1877/152206) while in subpopulation AFR AF = 0.0421 (1750/41542). AF 95% confidence interval is 0.0405. There are 36 homozygotes in GnomAd4. There are 843 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 36 AR gene

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LIFR	NM_001127671.2	MANE Select	c.*6316C>T	3_prime_UTR	Exon 20 of 20	NP_001121143.1	P42702-1
LIFR	NM_001364297.2		c.*6316C>T	3_prime_UTR	Exon 20 of 20	NP_001351226.1	P42702-1
LIFR	NM_002310.6		c.*6316C>T	3_prime_UTR	Exon 20 of 20	NP_002301.1	P42702-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LIFR	ENST00000453190.7	TSL:2 MANE Select	c.*6316C>T	3_prime_UTR	Exon 20 of 20	ENSP00000398368.2	P42702-1
LIFR	ENST00000263409.8	TSL:1	c.*6316C>T	3_prime_UTR	Exon 20 of 20	ENSP00000263409.4	P42702-1
LIFR	ENST00000929709.1		c.*6316C>T	3_prime_UTR	Exon 20 of 20	ENSP00000599768.1

Frequencies

GnomAD3 genomes

AF:

0.0124

AC:

1880

AN:

152088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0423

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00668

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00670

GnomAD4 exome

AF:

0.00182

AC:

AN:

41722

Hom.:

Cov.:

AF XY:

0.00133

AC XY:

AN XY:

19502

show subpopulations

African (AFR)

AF:

0.0317

AC:

AN:

1734

American (AMR)

AF:

0.00621

AC:

AN:

1128

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2588

East Asian (EAS)

AF:

0.00

AC:

AN:

6964

South Asian (SAS)

AF:

0.00

AC:

AN:

380

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

264

European-Non Finnish (NFE)

AF:

0.0000398

AC:

AN:

25096

Other (OTH)

AF:

0.00375

AC:

AN:

3470

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0123

AC:

1877

AN:

152206

Hom.:

Cov.:

AF XY:

0.0113

AC XY:

843

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.0421

AC:

1750

AN:

41542

American (AMR)

AF:

0.00667

AC:

102

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000414

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000132

AC:

AN:

67958

Other (OTH)

AF:

0.00663

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

184

277

369

461

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00674

Hom.:

Bravo

AF:

0.0145

Asia WGS

AF:

0.00376

AC:

AN:

3476

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Stuve-Wiedemann syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

6.5

(source)

DANN

Benign

0.67

PhyloP100

-0.034

Mutation Taster

=100/0

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over