Menu
GeneBe

12-6385074-A-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_002342.3(LTBR):c.246A>G(p.Thr82=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0104 in 1,614,226 control chromosomes in the GnomAD database, including 98 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0072 ( 6 hom., cov: 32)
Exomes 𝑓: 0.011 ( 92 hom. )

Consequence

LTBR
NM_002342.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.21
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 -11 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=-0.94).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 12-6385074-A-G is Benign according to our data. Variant chr12-6385074-A-G is described in ClinVar as [Benign]. Clinvar id is 773257.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=-1.21 with no splicing effect.
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 1097 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LTBRNM_002342.3 linkuse as main transcriptc.246A>G p.Thr82= synonymous_variant 3/10 ENST00000228918.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LTBRENST00000228918.9 linkuse as main transcriptc.246A>G p.Thr82= synonymous_variant 3/101 NM_002342.3 P2P36941-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00721
AC:
1097
AN:
152220
Hom.:
6
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00162
Gnomad AMI
AF:
0.00219
Gnomad AMR
AF:
0.00445
Gnomad ASJ
AF:
0.00749
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00289
Gnomad FIN
AF:
0.0173
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0106
Gnomad OTH
AF:
0.00669
GnomAD3 exomes
AF:
0.00822
AC:
2067
AN:
251494
Hom.:
3
AF XY:
0.00800
AC XY:
1087
AN XY:
135922
show subpopulations
Gnomad AFR exome
AF:
0.00117
Gnomad AMR exome
AF:
0.00194
Gnomad ASJ exome
AF:
0.00853
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.00389
Gnomad FIN exome
AF:
0.0188
Gnomad NFE exome
AF:
0.0116
Gnomad OTH exome
AF:
0.00814
GnomAD4 exome
AF:
0.0107
AC:
15661
AN:
1461888
Hom.:
92
Cov.:
32
AF XY:
0.0105
AC XY:
7632
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.00134
Gnomad4 AMR exome
AF:
0.00237
Gnomad4 ASJ exome
AF:
0.00849
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.00432
Gnomad4 FIN exome
AF:
0.0173
Gnomad4 NFE exome
AF:
0.0121
Gnomad4 OTH exome
AF:
0.00949
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00720
AC:
1097
AN:
152338
Hom.:
6
Cov.:
32
AF XY:
0.00721
AC XY:
537
AN XY:
74496
show subpopulations
Gnomad4 AFR
AF:
0.00161
Gnomad4 AMR
AF:
0.00444
Gnomad4 ASJ
AF:
0.00749
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00290
Gnomad4 FIN
AF:
0.0173
Gnomad4 NFE
AF:
0.0106
Gnomad4 OTH
AF:
0.00662
Alfa
AF:
0.00882
Hom.:
7
Bravo
AF:
0.00644
Asia WGS
AF:
0.00144
AC:
5
AN:
3478
EpiCase
AF:
0.00960
EpiControl
AF:
0.00883

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 testingInvitaeJun 23, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.94
Cadd
Benign
0.57
Dann
Benign
0.49
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs41480749; hg19: chr12-6494240; COSMIC: COSV57438960; COSMIC: COSV57438960; API