Genetic Variant LTBR:p.Glu52Asp (chr12-6384647-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002342.3(LTBR):c.156G>C(p.Glu52Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. E52E) has been classified as Benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

LTBR
NM_002342.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.147

Publications

0 publications found

Variant links:

Genes affected

LTBR (HGNC:6718): (lymphotoxin beta receptor) This gene encodes a member of the tumor necrosis factor receptor superfamily. The major ligands of this receptor include lymphotoxin alpha/beta and tumor necrosis factor ligand superfamily member 14. The encoded protein plays a role in signalling during the development of lymphoid and other organs, lipid metabolism, immune response, and programmed cell death. Activity of this receptor has also been linked to carcinogenesis. Alternatively spliced transcript variants encoding multiple isoforms have been observed. [provided by RefSeq, Aug 2012]

LTBR links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07922357).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002342.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LTBR	NM_002342.3	MANE Select	c.156G>C	p.Glu52Asp	missense	Exon 2 of 10	NP_002333.1	P36941-1
LTBR	NM_001414303.1		c.156G>C	p.Glu52Asp	missense	Exon 2 of 10	NP_001401232.1
LTBR	NM_001414304.1		c.156G>C	p.Glu52Asp	missense	Exon 2 of 10	NP_001401233.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LTBR	ENST00000228918.9	TSL:1 MANE Select	c.156G>C	p.Glu52Asp	missense	Exon 2 of 10	ENSP00000228918.4	P36941-1
LTBR	ENST00000884044.1		c.156G>C	p.Glu52Asp	missense	Exon 2 of 10	ENSP00000554103.1
LTBR	ENST00000957634.1		c.156G>C	p.Glu52Asp	missense	Exon 2 of 10	ENSP00000627693.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461876

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112004

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.0034

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.36

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.071

LIST_S2

Benign

0.63

M_CAP

Uncertain

0.24

MetaRNN

Benign

0.079

MetaSVM

Benign

-0.43

MutationAssessor

Benign

1.1

PhyloP100

0.15

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.3

REVEL

Benign

0.085

Sift

Benign

0.24

Sift4G

Pathogenic

0.0

Polyphen

0.018

Vest4

0.10

MutPred

0.37

Gain of phosphorylation at Y51 (P = 0.1421)

MVP

0.76

MPC

1.0

ClinPred

0.11

GERP RS

1.6

PromoterAI

0.039

Neutral

(source)

Varity_R

0.22

gMVP

0.79

Mutation Taster

=87/13

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over