Variant 11-65557854-CCAGCAGCAGCAGCAGCAGCAG-CCAGCAGCAGCAGCAGCAGCAGCAGCAG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

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 Benign (★★).

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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 11-65557854-C-CCAGCAG is Benign according to our data. Variant chr11-65557854-C-CCAGCAG is described in ClinVar as [Benign]. Clinvar id is 403062.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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/exons	MANE	Protein	UniProt
LTBP3	NM_001130144.3 linkuse as main transcript	c.100_105dupCTGCTG	p.Leu34_Leu35dup	conservative_inframe_insertion	1/28	ENST00000301873.11	NP_001123616.1	Q9NS15-1Q8WYU6
LTBP3	NM_021070.4 linkuse as main transcript	c.100_105dupCTGCTG	p.Leu34_Leu35dup	conservative_inframe_insertion	1/27		NP_066548.2	Q9NS15-2Q8WYU6
LTBP3	NM_001164266.1 linkuse as main transcript	c.-248_-243dupCTGCTG		5_prime_UTR_variant	1/27		NP_001157738.1	Q9NS15B9EG76Q8WYU6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LTBP3	ENST00000301873.11 linkuse as main transcript	c.100_105dupCTGCTG	p.Leu34_Leu35dup	conservative_inframe_insertion	1/28	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

GnomAD3 exomes

AF:

0.0772

AC:

2549

AN:

33030

Hom.:

AF XY:

0.0816

AC XY:

1564

AN XY:

19164

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 SAS exome

AF:

0.0610

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

Gnomad4 AFR exome

AF:

0.0412

Gnomad4 AMR exome

AF:

0.114

Gnomad4 ASJ exome

AF:

0.124

Gnomad4 EAS exome

AF:

0.0536

Gnomad4 SAS exome

AF:

0.0804

Gnomad4 FIN exome

AF:

0.0926

Gnomad4 NFE exome

AF:

0.171

Gnomad4 OTH exome

AF:

0.141

GnomAD4 genome

AF:

0.124

AC:

18545

AN:

149218

Hom.:

1439

Cov.:

AF XY:

0.118

AC XY:

8597

AN XY:

72830

show subpopulations

Gnomad4 AFR

AF:

0.0497

Gnomad4 AMR

AF:

0.124

Gnomad4 ASJ

AF:

0.143

Gnomad4 EAS

AF:

0.0282

Gnomad4 SAS

AF:

0.0933

Gnomad4 FIN

AF:

0.0948

Gnomad4 NFE

AF:

0.181

Gnomad4 OTH

AF:

0.121

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

Uncertain significance, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Feb 02, 2024

- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

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

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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