Genetic Variant LTB:c.208+35A>C (chr6-31581779-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002341.2(LTB):c.208+35A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0646 in 1,611,984 control chromosomes in the GnomAD database, including 3,821 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.066 ( 351 hom., cov: 32)

Exomes 𝑓: 0.064 ( 3470 hom. )

Consequence

LTB
NM_002341.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.259

Publications

22 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTB	NM_002341.2 link	c.208+35A>C		intron_variant	Intron 2 of 3	ENST00000429299.3	NP_002332.1	Q06643-1Q5STB2
LTB	NM_009588.1 link	c.163-149A>C		intron_variant	Intron 1 of 2		NP_033666.1	Q06643-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
LTB	ENST00000429299.3 link	c.208+35A>C	intron_variant	Intron 2 of 3	1	NM_002341.2	ENSP00000410481.3	Q06643-1
LTB	ENST00000446745.2 link	c.163-149A>C	intron_variant	Intron 1 of 2	1		ENSP00000416113.2	Q06643-2
LTB	ENST00000482429.1 link	n.628A>C	non_coding_transcript_exon_variant	Exon 1 of 2	2
LTB	ENST00000483972.1 link	n.28-149A>C	intron_variant	Intron 1 of 2	5

Frequencies

GnomAD3 genomes

AF:

0.0656

AC:

9973

AN:

151918

Hom.:

348

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0725

Gnomad AMI

AF:

0.185

Gnomad AMR

AF:

0.0618

Gnomad ASJ

AF:

0.122

Gnomad EAS

AF:

0.0347

Gnomad SAS

AF:

0.0838

Gnomad FIN

AF:

0.0181

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.0656

Gnomad OTH

AF:

0.0790

GnomAD2 exomes

AF:

0.0604

AC:

14856

AN:

245890

AF XY:

0.0627

show subpopulations

Gnomad AFR exome

AF:

0.0715

Gnomad AMR exome

AF:

0.0540

Gnomad ASJ exome

AF:

0.124

Gnomad EAS exome

AF:

0.0320

Gnomad FIN exome

AF:

0.0175

Gnomad NFE exome

AF:

0.0634

Gnomad OTH exome

AF:

0.0624

GnomAD4 exome

AF:

0.0645

AC:

94148

AN:

1459948

Hom.:

3470

Cov.:

AF XY:

0.0653

AC XY:

47421

AN XY:

726296

show subpopulations

African (AFR)

AF:

0.0710

AC:

2375

AN:

33460

American (AMR)

AF:

0.0568

AC:

2537

AN:

44642

Ashkenazi Jewish (ASJ)

AF:

0.127

AC:

3315

AN:

26070

East Asian (EAS)

AF:

0.0284

AC:

1127

AN:

39698

South Asian (SAS)

AF:

0.0780

AC:

6721

AN:

86218

European-Finnish (FIN)

AF:

0.0218

AC:

1140

AN:

52278

Middle Eastern (MID)

AF:

0.0909

AC:

524

AN:

5764

European-Non Finnish (NFE)

AF:

0.0646

AC:

71795

AN:

1111490

Other (OTH)

AF:

0.0765

AC:

4614

AN:

60328

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

4512

9024

13536

18048

22560

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2742

5484

8226

10968

13710

<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:

0.0658

AC:

9997

AN:

152036

Hom.:

351

Cov.:

AF XY:

0.0642

AC XY:

4774

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.0730

AC:

3026

AN:

41446

American (AMR)

AF:

0.0618

AC:

945

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.122

AC:

422

AN:

3468

East Asian (EAS)

AF:

0.0347

AC:

179

AN:

5152

South Asian (SAS)

AF:

0.0831

AC:

400

AN:

4816

European-Finnish (FIN)

AF:

0.0181

AC:

192

AN:

10592

Middle Eastern (MID)

AF:

0.139

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0656

AC:

4458

AN:

67956

Other (OTH)

AF:

0.0782

AC:

165

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

478

956

1433

1911

2389

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

228

342

456

570

<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:

0.0357

Hom.:

172

Bravo

AF:

0.0695

Asia WGS

AF:

0.0600

AC:

207

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

(source)

DANN

Benign

0.79

PhyloP100

-0.26

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over