6-31580980-C-G

Position:

chr6-31580980-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_002341.2(LTB):c.464G>C(p.Arg155Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000992 in 1,411,368 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000099 ( 0 hom. )

Consequence

LTB
NM_002341.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.10

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]

LTB links:

LTB (HGNC:):

LTB links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11151323).

BP6

Variant 6-31580980-C-G is Benign according to our data. Variant chr6-31580980-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3121378.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LTB	NM_002341.2 linkuse as main transcript	c.464G>C	p.Arg155Pro	missense_variant	4/4	ENST00000429299.3	NP_002332.1	Q06643-1Q5STB2
LTB	NM_009588.1 linkuse as main transcript	c.*184G>C		3_prime_UTR_variant	3/3		NP_033666.1	Q06643-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LTB	ENST00000429299.3 linkuse as main transcript	c.464G>C	p.Arg155Pro	missense_variant	4/4	1	NM_002341.2	ENSP00000410481.3	Q06643-1
LTB	ENST00000446745.2 linkuse as main transcript	c.*184G>C		3_prime_UTR_variant	3/3	1		ENSP00000416113.2	Q06643-2
LTB	ENST00000482429.1 linkuse as main transcript	n.1032G>C		non_coding_transcript_exon_variant	2/2	2
LTB	ENST00000483972.1 linkuse as main transcript	n.283G>C		non_coding_transcript_exon_variant	3/3	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000682

AC:

AN:

161226

Hom.:

AF XY:

0.0000568

AC XY:

AN XY:

88078

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000430

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

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:

0.00000992

AC:

AN:

1411368

Hom.:

Cov.:

AF XY:

0.00000860

AC XY:

AN XY:

697872

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000352

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000171

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000264

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 23, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Uncertain

0.59

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.023

M_CAP

Benign

0.011

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.6

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-1.3

REVEL

Benign

0.081

Sift

Benign

0.27

Sift4G

Benign

0.25

Polyphen

0.0010

Vest4

0.086

MutPred

0.56

Loss of MoRF binding (P = 0.0094);

MVP

0.41

MPC

1.9

ClinPred

0.060

GERP RS

-2.3

Varity_R

0.63

gMVP

0.65

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over