dbSNP rs41441750: LTBR:c.97-9C>T (chr12-6384579-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002342.3(LTBR):c.97-9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00154 in 1,613,382 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0081 ( 13 hom., cov: 33)

Exomes 𝑓: 0.00085 ( 8 hom. )

Consequence

LTBR
NM_002342.3 intron

Scores

Splicing: ADA: 0.0006929

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.04

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 12-6384579-C-T is Benign according to our data. Variant chr12-6384579-C-T is described in ClinVar as Benign. ClinVar VariationId is 726797.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00813 (1238/152348) while in subpopulation AFR AF = 0.0273 (1137/41584). AF 95% confidence interval is 0.026. There are 13 homozygotes in GnomAd4. There are 608 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 1238 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	Effect	Exon Rank	Protein	UniProt
LTBR	NM_002342.3	MANE Select	c.97-9C>T	intron	N/A	NP_002333.1	P36941-1
LTBR	NM_001414303.1		c.97-9C>T	intron	N/A	NP_001401232.1
LTBR	NM_001414304.1		c.97-9C>T	intron	N/A	NP_001401233.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LTBR	ENST00000228918.9	TSL:1 MANE Select	c.97-9C>T	intron	N/A	ENSP00000228918.4	P36941-1
LTBR	ENST00000884044.1		c.97-9C>T	intron	N/A	ENSP00000554103.1
LTBR	ENST00000957634.1		c.97-9C>T	intron	N/A	ENSP00000627693.1

Frequencies

GnomAD3 genomes

AF:

0.00810

AC:

1233

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0273

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00523

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:

0.000176

Gnomad OTH

AF:

0.00430

GnomAD2 exomes

AF:

0.00223

AC:

561

AN:

251060

AF XY:

0.00167

show subpopulations

Gnomad AFR exome

AF:

0.0277

Gnomad AMR exome

AF:

0.00229

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000167

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.000853

AC:

1246

AN:

1461034

Hom.:

Cov.:

AF XY:

0.000761

AC XY:

553

AN XY:

726868

show subpopulations

African (AFR)

AF:

0.0280

AC:

936

AN:

33470

American (AMR)

AF:

0.00233

AC:

104

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.000104

AC:

AN:

86236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00156

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000522

AC:

AN:

1111234

Other (OTH)

AF:

0.00215

AC:

130

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

144

216

288

360

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<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:

0.00813

AC:

1238

AN:

152348

Hom.:

Cov.:

AF XY:

0.00816

AC XY:

608

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.0273

AC:

1137

AN:

41584

American (AMR)

AF:

0.00523

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000176

AC:

AN:

68026

Other (OTH)

AF:

0.00425

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

129

194

258

323

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00383

Hom.:

Bravo

AF:

0.00935

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000178

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

9.2

(source)

DANN

Benign

0.83

PhyloP100

1.0

PromoterAI

-0.0087

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00069

dbscSNV1_RF

Benign

0.010

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