chr11-65557854-C-CCAGCAG

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP3BP6BA1

The NM_001130144.3(LTBP3):c.100_105dupCTGCTG(p.Leu34_Leu35dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 1,318,248 control chromosomes in the GnomAD database, including 7,553 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.12 ( 1439 hom., cov: 27)

Exomes 𝑓: 0.16 ( 6114 hom. )

Consequence

LTBP3
NM_001130144.3 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 0.342

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 -10 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001130144.3

BP6

Variant 11-65557854-C-CCAGCAG is Benign according to our data. Variant chr11-65557854-C-CCAGCAG is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 403062.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTBP3	NM_001130144.3 link	c.100_105dupCTGCTG	p.Leu34_Leu35dup	conservative_inframe_insertion	Exon 1 of 28	ENST00000301873.11	NP_001123616.1	Q9NS15-1Q8WYU6
LTBP3	NM_021070.4 link	c.100_105dupCTGCTG	p.Leu34_Leu35dup	conservative_inframe_insertion	Exon 1 of 27		NP_066548.2	Q9NS15-2Q8WYU6
LTBP3	NM_001164266.1 link	c.-248_-243dupCTGCTG		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.100_105dupCTGCTG	p.Leu34_Leu35dup	conservative_inframe_insertion	Exon 1 of 28	2	NM_001130144.3	ENSP00000301873.5		Q9NS15-1

Frequencies

GnomAD3 genomes

AF:

0.124

AC:

18558

AN:

149128

Hom.:

1441

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0498

Gnomad AMI

AF:

0.270

Gnomad AMR

AF:

0.124

Gnomad ASJ

AF:

0.143

Gnomad EAS

AF:

0.0279

Gnomad SAS

AF:

0.0934

Gnomad FIN

AF:

0.0948

Gnomad MID

AF:

0.218

Gnomad NFE

AF:

0.181

Gnomad OTH

AF:

0.123

GnomAD2 exomes

AF:

0.0772

AC:

2549

AN:

33030

AF XY:

0.0816

show subpopulations

Gnomad AFR exome

AF:

0.0240

Gnomad AMR exome

AF:

0.0534

Gnomad ASJ exome

AF:

0.0733

Gnomad EAS exome

AF:

0.00402

Gnomad FIN exome

AF:

0.0637

Gnomad NFE exome

AF:

0.107

Gnomad OTH exome

AF:

0.0850

GnomAD4 exome

AF:

0.158

AC:

184412

AN:

1169030

Hom.:

6114

Cov.:

AF XY:

0.157

AC XY:

89622

AN XY:

571230

show subpopulations

African (AFR)

AF:

0.0412

AC:

987

AN:

23974

American (AMR)

AF:

0.114

AC:

2191

AN:

19186

Ashkenazi Jewish (ASJ)

AF:

0.124

AC:

2189

AN:

17666

East Asian (EAS)

AF:

0.0536

AC:

1363

AN:

25424

South Asian (SAS)

AF:

0.0804

AC:

3856

AN:

47976

European-Finnish (FIN)

AF:

0.0926

AC:

2447

AN:

26426

Middle Eastern (MID)

AF:

0.149

AC:

567

AN:

3816

European-Non Finnish (NFE)

AF:

0.171

AC:

164208

AN:

957742

Other (OTH)

AF:

0.141

AC:

6604

AN:

46820

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

6813

13625

20438

27250

34063

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6850

13700

20550

27400

34250

<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:

0.124

AC:

18545

AN:

149218

Hom.:

1439

Cov.:

AF XY:

0.118

AC XY:

8597

AN XY:

72830

show subpopulations

African (AFR)

AF:

0.0497

AC:

2038

AN:

41026

American (AMR)

AF:

0.124

AC:

1859

AN:

15040

Ashkenazi Jewish (ASJ)

AF:

0.143

AC:

489

AN:

3424

East Asian (EAS)

AF:

0.0282

AC:

144

AN:

5110

South Asian (SAS)

AF:

0.0933

AC:

446

AN:

4782

European-Finnish (FIN)

AF:

0.0948

AC:

918

AN:

9684

Middle Eastern (MID)

AF:

0.206

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.181

AC:

12099

AN:

66904

Other (OTH)

AF:

0.121

AC:

248

AN:

2054

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

773

1545

2318

3090

3863

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

206

412

618

824

1030

<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:

0.0364

Hom.:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Brachyolmia-amelogenesis imperfecta syndrome;C4540511:Geleophysic dysplasia 3

Uncertain:1

Feb 02, 2024

Fulgent Genetics, Fulgent Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Brachyolmia-amelogenesis imperfecta syndrome

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.34

Mutation Taster

=84/16

polymorphism (auto)

(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