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

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_001130144.3(LTBP3):c.103_105dupCTG(p.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 0.0213 in 1,302,838 control chromosomes in the GnomAD database, including 113 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 32 hom., cov: 27)

Exomes 𝑓: 0.022 ( 81 hom. )

Consequence

LTBP3
NM_001130144.3 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 11-65557854-C-CCAG is Benign according to our data. Variant chr11-65557854-C-CCAG is described in ClinVar as [Benign]. Clinvar id is 464024.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.019 (2833/149228) while in subpopulation AFR AF= 0.0245 (1005/41026). AF 95% confidence interval is 0.0232. There are 32 homozygotes in gnomad4. There are 1303 alleles in male gnomad4 subpopulation. Median coverage is 27. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 32 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LTBP3	NM_001130144.3 linkuse as main transcript	c.103_105dupCTG	p.Leu35dup	conservative_inframe_insertion	1/28	ENST00000301873.11	NP_001123616.1	Q9NS15-1Q8WYU6
LTBP3	NM_021070.4 linkuse as main transcript	c.103_105dupCTG	p.Leu35dup	conservative_inframe_insertion	1/27		NP_066548.2	Q9NS15-2Q8WYU6
LTBP3	NM_001164266.1 linkuse as main transcript	c.-245_-243dupCTG		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.103_105dupCTG	p.Leu35dup	conservative_inframe_insertion	1/28	2	NM_001130144.3	ENSP00000301873.5		Q9NS15-1

Frequencies

GnomAD3 genomes

AF:

0.0190

AC:

2828

AN:

149138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0244

Gnomad AMI

AF:

0.00661

Gnomad AMR

AF:

0.0176

Gnomad ASJ

AF:

0.00526

Gnomad EAS

AF:

0.00332

Gnomad SAS

AF:

0.00564

Gnomad FIN

AF:

0.00589

Gnomad MID

AF:

0.00325

Gnomad NFE

AF:

0.0206

Gnomad OTH

AF:

0.0280

GnomAD3 exomes

AF:

0.0509

AC:

1681

AN:

33030

Hom.:

AF XY:

0.0506

AC XY:

969

AN XY:

19164

show subpopulations

Gnomad AFR exome

AF:

0.0459

Gnomad AMR exome

AF:

0.0557

Gnomad ASJ exome

AF:

0.0540

Gnomad EAS exome

AF:

0.0121

Gnomad SAS exome

AF:

0.0366

Gnomad FIN exome

AF:

0.0327

Gnomad NFE exome

AF:

0.0596

Gnomad OTH exome

AF:

0.0723

GnomAD4 exome

AF:

0.0215

AC:

24860

AN:

1153610

Hom.:

Cov.:

AF XY:

0.0213

AC XY:

12032

AN XY:

563686

show subpopulations

Gnomad4 AFR exome

AF:

0.0227

Gnomad4 AMR exome

AF:

0.0183

Gnomad4 ASJ exome

AF:

0.00749

Gnomad4 EAS exome

AF:

0.00603

Gnomad4 SAS exome

AF:

0.00733

Gnomad4 FIN exome

AF:

0.00663

Gnomad4 NFE exome

AF:

0.0235

Gnomad4 OTH exome

AF:

0.0191

GnomAD4 genome

AF:

0.0190

AC:

2833

AN:

149228

Hom.:

Cov.:

AF XY:

0.0179

AC XY:

1303

AN XY:

72828

show subpopulations

Gnomad4 AFR

AF:

0.0245

Gnomad4 AMR

AF:

0.0175

Gnomad4 ASJ

AF:

0.00526

Gnomad4 EAS

AF:

0.00333

Gnomad4 SAS

AF:

0.00565

Gnomad4 FIN

AF:

0.00589

Gnomad4 NFE

AF:

0.0206

Gnomad4 OTH

AF:

0.0277

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -

not specified

Benign:1

Benign, no assertion criteria provided

clinical testing

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

- -

Brachyolmia-amelogenesis imperfecta syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 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