Variant 6-31581580-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_002341.2(LTB):c.259C>T(p.Leu87Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00165 in 1,612,988 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0052 ( 10 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 9 hom. )

Consequence

LTB
NM_002341.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.14

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009936571).

BP6

Variant 6-31581580-G-A is Benign according to our data. Variant chr6-31581580-G-A is described in ClinVar as [Benign]. Clinvar id is 778228.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LTB	NM_002341.2 linkuse as main transcript	c.259C>T	p.Leu87Phe	missense_variant	3/4	ENST00000429299.3	NP_002332.1	Q06643-1Q5STB2
LTB	NM_009588.1 linkuse as main transcript	c.213C>T	p.Gly71Gly	synonymous_variant	2/3		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.259C>T	p.Leu87Phe	missense_variant	3/4	1	NM_002341.2	ENSP00000410481.3	Q06643-1
LTB	ENST00000446745.2 linkuse as main transcript	c.213C>T	p.Gly71Gly	synonymous_variant	2/3	1		ENSP00000416113.2	Q06643-2
LTB	ENST00000482429.1 linkuse as main transcript	n.827C>T		non_coding_transcript_exon_variant	1/2	2
LTB	ENST00000483972.1 linkuse as main transcript	n.78C>T		non_coding_transcript_exon_variant	2/3	5

Frequencies

GnomAD3 genomes

AF:

0.00509

AC:

774

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0123

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00949

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00212

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00124

Gnomad OTH

AF:

0.00718

GnomAD3 exomes

AF:

0.00202

AC:

497

AN:

246584

Hom.:

AF XY:

0.00170

AC XY:

229

AN XY:

134406

show subpopulations

Gnomad AFR exome

AF:

0.0102

Gnomad AMR exome

AF:

0.00528

Gnomad ASJ exome

AF:

0.000201

Gnomad EAS exome

AF:

0.000219

Gnomad SAS exome

AF:

0.000198

Gnomad FIN exome

AF:

0.000324

Gnomad NFE exome

AF:

0.00117

Gnomad OTH exome

AF:

0.00214

GnomAD4 exome

AF:

0.00128

AC:

1876

AN:

1460740

Hom.:

Cov.:

AF XY:

0.00122

AC XY:

885

AN XY:

726682

show subpopulations

Gnomad4 AFR exome

AF:

0.0114

Gnomad4 AMR exome

AF:

0.00490

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.000353

Gnomad4 SAS exome

AF:

0.000267

Gnomad4 FIN exome

AF:

0.000401

Gnomad4 NFE exome

AF:

0.000934

Gnomad4 OTH exome

AF:

0.00234

GnomAD4 genome

AF:

0.00518

AC:

788

AN:

152248

Hom.:

Cov.:

AF XY:

0.00528

AC XY:

393

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.0126

Gnomad4 AMR

AF:

0.00948

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00212

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00124

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00130

Hom.:

Bravo

AF:

0.00586

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.0113

AC:

ESP6500EA

AF:

0.000739

AC:

ExAC

AF:

0.00171

AC:

201

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.000981

EpiControl

AF:

0.00178

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 submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

Eigen

Benign

0.13

Eigen_PC

Benign

0.18

FATHMM_MKL

Benign

0.58

MetaRNN

Benign

0.0099

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.1

REVEL

Benign

0.047

Sift

Benign

0.077

Sift4G

Benign

0.20

Polyphen

0.57

Vest4

0.40

MVP

0.59

MPC

0.45

ClinPred

0.016

GERP RS

4.1

Varity_R

0.29

gMVP

0.23

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