Genetic Variant NM_002342.3:c.35T>A (chr12-6384393-T-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_002342.3(LTBR):c.35T>A(p.Leu12Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000156 in 1,538,832 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

LTBR
NM_002342.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.16

Publications

0 publications found

Variant links:

Genes affected

LTBR (HGNC:6718): (lymphotoxin beta receptor) This gene encodes a member of the tumor necrosis factor receptor superfamily. The major ligands of this receptor include lymphotoxin alpha/beta and tumor necrosis factor ligand superfamily member 14. The encoded protein plays a role in signalling during the development of lymphoid and other organs, lipid metabolism, immune response, and programmed cell death. Activity of this receptor has also been linked to carcinogenesis. Alternatively spliced transcript variants encoding multiple isoforms have been observed. [provided by RefSeq, Aug 2012]

LTBR links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAdExome4 at 22 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002342.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LTBR	NM_002342.3	MANE Select	c.35T>A	p.Leu12Gln	missense	Exon 1 of 10	NP_002333.1	P36941-1
LTBR	NM_001414303.1		c.35T>A	p.Leu12Gln	missense	Exon 1 of 10	NP_001401232.1
LTBR	NM_001414304.1		c.35T>A	p.Leu12Gln	missense	Exon 1 of 10	NP_001401233.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LTBR	ENST00000228918.9	TSL:1 MANE Select	c.35T>A	p.Leu12Gln	missense	Exon 1 of 10	ENSP00000228918.4	P36941-1
LTBR	ENST00000884044.1		c.35T>A	p.Leu12Gln	missense	Exon 1 of 10	ENSP00000554103.1
LTBR	ENST00000957634.1		c.35T>A	p.Leu12Gln	missense	Exon 1 of 10	ENSP00000627693.1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

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

GnomAD2 exomes

AF:

0.000155

AC:

AN:

135832

AF XY:

0.0000812

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000858

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.0000159

AC:

AN:

1386608

Hom.:

Cov.:

AF XY:

0.00000877

AC XY:

AN XY:

684378

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31640

American (AMR)

AF:

0.000617

AC:

AN:

35662

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25110

East Asian (EAS)

AF:

0.00

AC:

AN:

35848

South Asian (SAS)

AF:

0.00

AC:

AN:

79236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37338

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5162

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1078818

Other (OTH)

AF:

0.00

AC:

AN:

57794

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152224

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41458

American (AMR)

AF:

0.000131

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.0000298

Hom.:

Bravo

AF:

0.0000491

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Uncertain

0.014

BayesDel_noAF

Pathogenic

0.17

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.35

Eigen

Uncertain

0.24

Eigen_PC

Benign

0.18

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.78

M_CAP

Pathogenic

0.81

MetaRNN

Uncertain

0.47

MetaSVM

Uncertain

0.35

MutationAssessor

Benign

1.9

PhyloP100

2.2

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-1.9

REVEL

Pathogenic

0.69

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.71

MVP

0.87

MPC

2.2

ClinPred

0.12

GERP RS

3.4

PromoterAI

-0.017

Neutral

(source)

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.2

Varity_R

0.37

gMVP

0.78

Mutation Taster

=70/30

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over