Genetic Variant NM_001130144.3:c.97_105delCTGCTGCTG (chr11-65557854-CCAGCAGCAG-C) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP3BP6_ModerateBA1

The NM_001130144.3(LTBP3):c.97_105delCTGCTGCTG(p.Leu33_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 0.00459 in 1,320,212 control chromosomes in the GnomAD database, including 226 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.024 ( 163 hom., cov: 27)

Exomes 𝑓: 0.0021 ( 63 hom. )

Consequence

LTBP3
NM_001130144.3 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.541

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: Benign. The variant received -11 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001130144.3

BP6

Variant 11-65557854-CCAGCAGCAG-C is Benign according to our data. Variant chr11-65557854-CCAGCAGCAG-C is described in ClinVar as Likely_benign. ClinVar VariationId is 464028.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTBP3	NM_001130144.3 link	c.97_105delCTGCTGCTG	p.Leu33_Leu35del	conservative_inframe_deletion	Exon 1 of 28	ENST00000301873.11	NP_001123616.1	Q9NS15-1Q8WYU6
LTBP3	NM_021070.4 link	c.97_105delCTGCTGCTG	p.Leu33_Leu35del	conservative_inframe_deletion	Exon 1 of 27		NP_066548.2	Q9NS15-2Q8WYU6
LTBP3	NM_001164266.1 link	c.-251_-243delCTGCTGCTG		5_prime_UTR_variant	Exon 1 of 27		NP_001157738.1	Q9NS15B9EG76Q8WYU6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTBP3	ENST00000301873.11 link	c.97_105delCTGCTGCTG	p.Leu33_Leu35del	conservative_inframe_deletion	Exon 1 of 28	2	NM_001130144.3	ENSP00000301873.5		Q9NS15-1

Frequencies

GnomAD3 genomes

AF:

0.0242

AC:

3611

AN:

149144

Hom.:

162

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0834

Gnomad AMI

AF:

0.00330

Gnomad AMR

AF:

0.00805

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.00167

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00325

Gnomad NFE

AF:

0.000553

Gnomad OTH

AF:

0.0147

GnomAD2 exomes

AF:

0.000454

AC:

AN:

33030

AF XY:

0.000209

show subpopulations

Gnomad AFR exome

AF:

0.0175

Gnomad AMR exome

AF:

0.000304

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000321

Gnomad OTH exome

AF:

0.000977

GnomAD4 exome

AF:

0.00210

AC:

2454

AN:

1170978

Hom.:

AF XY:

0.00187

AC XY:

1070

AN XY:

572162

show subpopulations

African (AFR)

AF:

0.0765

AC:

1831

AN:

23944

American (AMR)

AF:

0.00271

AC:

AN:

19192

Ashkenazi Jewish (ASJ)

AF:

0.0000565

AC:

AN:

17700

East Asian (EAS)

AF:

0.000236

AC:

AN:

25430

South Asian (SAS)

AF:

0.000521

AC:

AN:

47984

European-Finnish (FIN)

AF:

0.00

AC:

AN:

26432

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

3822

European-Non Finnish (NFE)

AF:

0.000339

AC:

325

AN:

959600

Other (OTH)

AF:

0.00429

AC:

201

AN:

46874

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

100

201

301

402

502

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

160

240

320

400

<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:

0.0242

AC:

3609

AN:

149234

Hom.:

163

Cov.:

AF XY:

0.0236

AC XY:

1718

AN XY:

72838

show subpopulations

African (AFR)

AF:

0.0831

AC:

3408

AN:

41014

American (AMR)

AF:

0.00804

AC:

121

AN:

15046

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3424

East Asian (EAS)

AF:

0.000196

AC:

AN:

5110

South Asian (SAS)

AF:

0.00167

AC:

AN:

4782

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9686

Middle Eastern (MID)

AF:

0.00350

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.000553

AC:

AN:

66922

Other (OTH)

AF:

0.0146

AC:

AN:

2056

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

158

315

473

630

788

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

144

180

<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

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Brachyolmia-amelogenesis imperfecta syndrome

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.54

Mutation Taster

=196/4

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over