Genetic Variant LTBP1:p.Pro106del (chr2-32947621-ACCG-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_206943.4(LTBP1):c.316_318delCCG(p.Pro106del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000707 in 1,162,572 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00071 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LTBP1
NM_206943.4 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.14

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTBP1	NM_206943.4 link	c.316_318delCCG	p.Pro106del	conservative_inframe_deletion	Exon 1 of 34	ENST00000404816.7	NP_996826.3	Q14766-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTBP1	ENST00000404816.7 link	c.316_318delCCG	p.Pro106del	conservative_inframe_deletion	Exon 1 of 34	5	NM_206943.4	ENSP00000386043.2		Q14766-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

150372

Hom.:

Cov.:

FAILED QC

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:

0.0000992

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000594

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00544

AC:

AN:

8816

Hom.:

AF XY:

0.00660

AC XY:

AN XY:

5304

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00483

Gnomad ASJ exome

AF:

0.0164

Gnomad EAS exome

AF:

0.0109

Gnomad SAS exome

AF:

0.00893

Gnomad FIN exome

AF:

0.00292

Gnomad NFE exome

AF:

0.00382

Gnomad OTH exome

AF:

0.0212

GnomAD4 exome

AF:

0.000707

AC:

822

AN:

1162572

Hom.:

AF XY:

0.000839

AC XY:

475

AN XY:

565980

show subpopulations

Gnomad4 AFR exome

AF:

0.000348

Gnomad4 AMR exome

AF:

0.00128

Gnomad4 ASJ exome

AF:

0.00152

Gnomad4 EAS exome

AF:

0.000285

Gnomad4 SAS exome

AF:

0.00519

Gnomad4 FIN exome

AF:

0.00196

Gnomad4 NFE exome

AF:

0.000464

Gnomad4 OTH exome

AF:

0.000685

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000333

AC:

AN:

150372

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73388

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000992

Gnomad4 NFE

AF:

0.0000594

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Cutis laxa, autosomal recessive, type 2E

Uncertain:1

Dec 13, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over