Genetic Variant LTBP1:p.Thr132dup (chr2-32947716-T-TCAC) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PM4_Supporting

The NM_206943.4(LTBP1):c.395_397dupCCA(p.Thr132dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000313 in 1,534,598 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

LTBP1
NM_206943.4 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.717

Publications

0 publications found

Variant links:

Genes affected

LTBP1 (HGNC:6714): (latent transforming growth factor beta binding protein 1) The protein encoded by this gene belongs to the family of latent TGF-beta binding proteins (LTBPs). The secretion and activation of TGF-betas is regulated by their association with latency-associated proteins and with latent TGF-beta binding proteins. The product of this gene targets latent complexes of transforming growth factor beta to the extracellular matrix, where the latent cytokine is subsequently activated by several different mechanisms. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

LTBP1 Gene-Disease associations (from GenCC):

cutis laxa, autosomal recessive, type 2E
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

LTBP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_206943.4. Strenght limited to Supporting due to length of the change: 1aa.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_206943.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTBP1	NM_206943.4	MANE Select	c.395_397dupCCA	p.Thr132dup	disruptive_inframe_insertion	Exon 1 of 34	NP_996826.3	Q14766-1
	LTBP1	NM_001394905.1		c.395_397dupCCA	p.Thr132dup	disruptive_inframe_insertion	Exon 1 of 34	NP_001381834.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LTBP1	ENST00000404816.7	TSL:5 MANE Select	c.395_397dupCCA	p.Thr132dup	disruptive_inframe_insertion	Exon 1 of 34	ENSP00000386043.2	Q14766-1
LTBP1	ENST00000929169.1		c.395_397dupCCA	p.Thr132dup	disruptive_inframe_insertion	Exon 1 of 34	ENSP00000599228.1
LTBP1	ENST00000954823.1		c.395_397dupCCA	p.Thr132dup	disruptive_inframe_insertion	Exon 1 of 34	ENSP00000624882.1

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

151896

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000236

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000299

AC:

AN:

167118

AF XY:

0.0000211

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000108

Gnomad NFE exome

AF:

0.0000411

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000231

AC:

AN:

1382702

Hom.:

Cov.:

AF XY:

0.0000218

AC XY:

AN XY:

686808

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28510

American (AMR)

AF:

0.00

AC:

AN:

35106

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23948

East Asian (EAS)

AF:

0.00

AC:

AN:

31494

South Asian (SAS)

AF:

0.00

AC:

AN:

77522

European-Finnish (FIN)

AF:

0.000120

AC:

AN:

49920

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5520

European-Non Finnish (NFE)

AF:

0.0000242

AC:

AN:

1074218

Other (OTH)

AF:

0.00

AC:

AN:

56464

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

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:

0.000105

AC:

AN:

151896

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74198

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41404

American (AMR)

AF:

0.00

AC:

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10514

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000236

AC:

AN:

67932

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

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:

0.000864

Hom.:

Bravo

AF:

0.0000151

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.72

Mutation Taster

=82/18

polymorphism

(source)

Splicing

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