Menu
GeneBe

12-6384647-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_002342.3(LTBR):c.156G>A(p.Glu52=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000615 in 1,614,230 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00068 ( 3 hom., cov: 33)
Exomes 𝑓: 0.00061 ( 5 hom. )

Consequence

LTBR
NM_002342.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.147
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.69).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 12-6384647-G-A is Benign according to our data. Variant chr12-6384647-G-A is described in ClinVar as [Benign]. Clinvar id is 779945.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.147 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000683 (104/152356) while in subpopulation EAS AF= 0.0187 (97/5182). AF 95% confidence interval is 0.0157. There are 3 homozygotes in gnomad4. There are 61 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 104 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LTBRNM_002342.3 linkuse as main transcriptc.156G>A p.Glu52= synonymous_variant 2/10 ENST00000228918.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LTBRENST00000228918.9 linkuse as main transcriptc.156G>A p.Glu52= synonymous_variant 2/101 NM_002342.3 P2P36941-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000683
AC:
104
AN:
152238
Hom.:
3
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.0187
Gnomad SAS
AF:
0.00124
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.00144
AC:
361
AN:
251394
Hom.:
6
AF XY:
0.00127
AC XY:
172
AN XY:
135894
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000578
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0185
Gnomad SAS exome
AF:
0.000425
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.000489
GnomAD4 exome
AF:
0.000607
AC:
888
AN:
1461874
Hom.:
5
Cov.:
32
AF XY:
0.000593
AC XY:
431
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0189
Gnomad4 SAS exome
AF:
0.000487
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.00147
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000683
AC:
104
AN:
152356
Hom.:
3
Cov.:
33
AF XY:
0.000819
AC XY:
61
AN XY:
74512
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.0187
Gnomad4 SAS
AF:
0.00124
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000241
Hom.:
0
Bravo
AF:
0.00116
Asia WGS
AF:
0.00635
AC:
22
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 05, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.69
Cadd
Benign
7.9
Dann
Benign
0.88
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs11555387; hg19: chr12-6493813; API