6-31582374-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_002341.2(LTB):​c.44G>A​(p.Gly15Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000924 in 1,612,912 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000094 ( 2 hom. )

Consequence

LTB
NM_002341.2 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.882
Variant links:
Genes affected
LTB (HGNC:6711): (lymphotoxin beta) Lymphotoxin beta is a type II membrane protein of the TNF family. It anchors lymphotoxin-alpha to the cell surface through heterotrimer formation. The predominant form on the lymphocyte surface is the lymphotoxin-alpha 1/beta 2 complex (e.g. 1 molecule alpha/2 molecules beta) and this complex is the primary ligand for the lymphotoxin-beta receptor. The minor complex is lymphotoxin-alpha 2/beta 1. LTB is an inducer of the inflammatory response system and involved in normal development of lymphoid tissue. Lymphotoxin-beta isoform b is unable to complex with lymphotoxin-alpha suggesting a function for lymphotoxin-beta which is independent of lympyhotoxin-alpha. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.018257946).
BS2
High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LTBNM_002341.2 linkc.44G>A p.Gly15Glu missense_variant Exon 1 of 4 ENST00000429299.3 NP_002332.1 Q06643-1Q5STB2
LTBNM_009588.1 linkc.44G>A p.Gly15Glu missense_variant Exon 1 of 3 NP_033666.1 Q06643-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LTBENST00000429299.3 linkc.44G>A p.Gly15Glu missense_variant Exon 1 of 4 1 NM_002341.2 ENSP00000410481.3 Q06643-1
LTBENST00000446745.2 linkc.44G>A p.Gly15Glu missense_variant Exon 1 of 3 1 ENSP00000416113.2 Q06643-2
LTBENST00000482429.1 linkn.33G>A non_coding_transcript_exon_variant Exon 1 of 2 2
LTBENST00000483972.1 linkn.27+122G>A intron_variant Intron 1 of 2 5

Frequencies

GnomAD3 genomes
AF:
0.0000723
AC:
11
AN:
152184
Hom.:
0
Cov.:
32
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:
0.00212
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000815
AC:
20
AN:
245548
Hom.:
0
AF XY:
0.0000747
AC XY:
10
AN XY:
133940
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00109
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000945
AC:
138
AN:
1460610
Hom.:
2
Cov.:
32
AF XY:
0.0000908
AC XY:
66
AN XY:
726610
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00343
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000722
AC:
11
AN:
152302
Hom.:
0
Cov.:
32
AF XY:
0.0000940
AC XY:
7
AN XY:
74468
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00212
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000189
ExAC
AF:
0.000102
AC:
12

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 23, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.44G>A (p.G15E) alteration is located in exon 1 (coding exon 1) of the LTB gene. This alteration results from a G to A substitution at nucleotide position 44, causing the glycine (G) at amino acid position 15 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.47
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
19
DANN
Uncertain
0.99
DEOGEN2
Benign
0.16
T;.
Eigen
Benign
0.064
Eigen_PC
Benign
0.15
FATHMM_MKL
Benign
0.60
D
LIST_S2
Benign
0.66
.;T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.018
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.7
L;L
PrimateAI
Benign
0.42
T
PROVEAN
Benign
-2.0
N;D
REVEL
Benign
0.029
Sift
Benign
0.22
T;D
Sift4G
Benign
0.29
T;D
Polyphen
0.23
B;.
Vest4
0.22
MutPred
0.31
Loss of sheet (P = 0.0126);Loss of sheet (P = 0.0126);
MVP
0.66
MPC
0.17
ClinPred
0.061
T
GERP RS
4.2
Varity_R
0.095
gMVP
0.52

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: rs563979837; hg19: chr6-31550151; COSMIC: COSV53002173; COSMIC: COSV53002173; API