rs2229699

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_002341.2(LTB):c.365C>T(p.Ala122Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0017 in 1,610,968 control chromosomes in the GnomAD database, including 33 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 Benign (★).

Frequency

Genomes: 𝑓 0.0022 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 29 hom. )

Consequence

LTB
NM_002341.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.63

Publications

7 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005446583).

BP6

Variant 6-31581079-G-A is Benign according to our data. Variant chr6-31581079-G-A is described in ClinVar as Benign. ClinVar VariationId is 770169.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTB	NM_002341.2 link	c.365C>T	p.Ala122Val	missense_variant	Exon 4 of 4	ENST00000429299.3	NP_002332.1	Q06643-1Q5STB2
LTB	NM_009588.1 link	c.*85C>T		3_prime_UTR_variant	Exon 3 of 3		NP_033666.1	Q06643-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LTB	ENST00000429299.3 link	c.365C>T	p.Ala122Val	missense_variant	Exon 4 of 4	1	NM_002341.2	ENSP00000410481.3	Q06643-1
LTB	ENST00000446745.2 link	c.*85C>T		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000416113.2	Q06643-2
LTB	ENST00000482429.1 link	n.933C>T		non_coding_transcript_exon_variant	Exon 2 of 2	2
LTB	ENST00000483972.1 link	n.184C>T		non_coding_transcript_exon_variant	Exon 3 of 3	5

Frequencies

GnomAD3 genomes

AF:

0.00222

AC:

338

AN:

152262

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00902

Gnomad ASJ

AF:

0.00662

Gnomad EAS

AF:

0.0133

Gnomad SAS

AF:

0.00848

Gnomad FIN

AF:

0.00216

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.00449

AC:

1077

AN:

240128

AF XY:

0.00394

show subpopulations

Gnomad AFR exome

AF:

0.000608

Gnomad AMR exome

AF:

0.0141

Gnomad ASJ exome

AF:

0.00614

Gnomad EAS exome

AF:

0.0162

Gnomad FIN exome

AF:

0.00113

Gnomad NFE exome

AF:

0.000479

Gnomad OTH exome

AF:

0.00202

GnomAD4 exome

AF:

0.00165

AC:

2402

AN:

1458588

Hom.:

Cov.:

AF XY:

0.00175

AC XY:

1273

AN XY:

725600

show subpopulations

African (AFR)

AF:

0.000419

AC:

AN:

33388

American (AMR)

AF:

0.0139

AC:

614

AN:

44248

Ashkenazi Jewish (ASJ)

AF:

0.00619

AC:

161

AN:

26008

East Asian (EAS)

AF:

0.0145

AC:

576

AN:

39632

South Asian (SAS)

AF:

0.00557

AC:

480

AN:

86130

European-Finnish (FIN)

AF:

0.00144

AC:

AN:

52134

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.000248

AC:

275

AN:

1111030

Other (OTH)

AF:

0.00340

AC:

205

AN:

60260

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

140

280

421

561

701

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00224

AC:

341

AN:

152380

Hom.:

Cov.:

AF XY:

0.00243

AC XY:

181

AN XY:

74520

show subpopulations

African (AFR)

AF:

0.000529

AC:

AN:

41592

American (AMR)

AF:

0.00914

AC:

140

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00662

AC:

AN:

3472

East Asian (EAS)

AF:

0.0133

AC:

AN:

5190

South Asian (SAS)

AF:

0.00849

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00216

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000220

AC:

AN:

68038

Other (OTH)

AF:

0.00378

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00165

Hom.:

Bravo

AF:

0.00255

ESP6500AA

AF:

0.000332

AC:

ESP6500EA

AF:

0.000185

AC:

ExAC

AF:

0.00396

AC:

462

Asia WGS

AF:

0.0150

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000830

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.55

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.64

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.059

MetaRNN

Benign

0.0054

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

PhyloP100

1.6

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.4

REVEL

Benign

0.049

Sift

Benign

0.079

Sift4G

Benign

0.19

Polyphen

0.19

Vest4

0.17

MVP

0.67

MPC

1.5

ClinPred

0.019

GERP RS

4.5

Varity_R

0.22

gMVP

0.29

Mutation Taster

=96/4

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over