Genetic Variant LTBP3:p.Leu30_Leu35del (chr11-65557854-CCAGCAGCAGCAGCAGCAG-C) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_001130144.3(LTBP3):c.88_105delCTGCTGCTGCTGCTGCTG(p.Leu30_Leu35del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000189 in 1,320,252 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 27)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

LTBP3
NM_001130144.3 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.773

Publications

4 publications found

Variant links:

Genes affected

LTBP3 (HGNC:6716): (latent transforming growth factor beta binding protein 3) The protein encoded by this gene forms a complex with transforming growth factor beta (TGF-beta) proteins and may be involved in their subcellular localization. Activation of this complex requires removal of the encoded binding protein. This protein also may play a structural role in the extracellular matrix. Three transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2010]

LTBP3 Gene-Disease associations (from GenCC):

brachyolmia-amelogenesis imperfecta syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
geleophysic dysplasia 3
Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
Acromicric dysplasia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
geleophysic dysplasia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

LTBP3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001130144.3

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130144.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
LTBP3	NM_001130144.3	MANE Select	c.88_105delCTGCTGCTGCTGCTGCTG	p.Leu30_Leu35del	conservative_inframe_deletion	Exon 1 of 28	NP_001123616.1
LTBP3	NM_021070.4		c.88_105delCTGCTGCTGCTGCTGCTG	p.Leu30_Leu35del	conservative_inframe_deletion	Exon 1 of 27	NP_066548.2
LTBP3	NM_001164266.1		c.-260_-243delCTGCTGCTGCTGCTGCTG		5_prime_UTR	Exon 1 of 27	NP_001157738.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
LTBP3	ENST00000301873.11	TSL:2 MANE Select	c.88_105delCTGCTGCTGCTGCTGCTG	p.Leu30_Leu35del	conservative_inframe_deletion	Exon 1 of 28	ENSP00000301873.5
LTBP3	ENST00000322147.8	TSL:1	c.88_105delCTGCTGCTGCTGCTGCTG	p.Leu30_Leu35del	conservative_inframe_deletion	Exon 1 of 27	ENSP00000326647.4
LTBP3	ENST00000528516.5	TSL:1	n.88_105delCTGCTGCTGCTGCTGCTG		non_coding_transcript_exon	Exon 1 of 27	ENSP00000432350.1

Frequencies

GnomAD3 genomes

AF:

0.0000134

AC:

AN:

149162

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:

0.000209

Gnomad FIN

AF:

0.000103

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000196

AC:

AN:

1171090

Hom.:

AF XY:

0.0000175

AC XY:

AN XY:

572214

show subpopulations

African (AFR)

AF:

0.0000834

AC:

AN:

23982

American (AMR)

AF:

0.00

AC:

AN:

19206

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17700

East Asian (EAS)

AF:

0.00

AC:

AN:

25430

South Asian (SAS)

AF:

0.0000208

AC:

AN:

48004

European-Finnish (FIN)

AF:

0.0000757

AC:

AN:

26434

Middle Eastern (MID)

AF:

0.000262

AC:

AN:

3822

European-Non Finnish (NFE)

AF:

0.0000177

AC:

AN:

959634

Other (OTH)

AF:

0.00

AC:

AN:

46878

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

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:

0.0000134

AC:

AN:

149162

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

72744

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40926

American (AMR)

AF:

0.00

AC:

AN:

15028

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3424

East Asian (EAS)

AF:

0.00

AC:

AN:

5126

South Asian (SAS)

AF:

0.000209

AC:

AN:

4788

European-Finnish (FIN)

AF:

0.000103

AC:

AN:

9686

Middle Eastern (MID)

AF:

0.00

AC:

AN:

308

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66932

Other (OTH)

AF:

0.00

AC:

AN:

2036

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

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:

0.00

Hom.:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Brachyolmia-amelogenesis imperfecta syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.77

Mutation Taster

=131/69

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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11-65557854-CCAGCAGCAGCAGCAGCAGCAG-CCAG

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