11-65557854-CCAGCAGCAGCAGCAGCAGCAG-CCAGCAGCAGCAGCAGCAG

Position:

• chr11-65557854-CCAGCAGCAGCAGCAGCAGCAG-CCAGCAGCAGCAGCAGCAG

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS1

The NM_001130144.3(LTBP3):​c.103_105delCTG​(p.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 0.016 in 1,220,450 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0023 (0 hom., cov: 27)
  • Exomes 𝑓: 0.018 (1 hom.)
• Consequence: LTBP3 NM_001130144.3 conservative_inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4 O:1
• Conservation: PhyloP100: 0.403

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP6: Variant 11-65557854-CCAG-C is Benign according to our data. Variant chr11-65557854-CCAG-C is described in ClinVar as [Likely_benign]. Clinvar id is 532697.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-65557854-CCAG-C is described in Lovd as [Likely_benign]. Variant chr11-65557854-CCAG-C is described in Lovd as [Benign]. Variant chr11-65557854-CCAG-C is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00229 (341/149142) while in subpopulation AFR AF= 0.00341 (140/41020). AF 95% confidence interval is 0.00295. There are 0 homozygotes in gnomad4. There are 176 alleles in male gnomad4 subpopulation. Median coverage is 27. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LTBP3	NM_001130144.3	c.103_105delCTG	p.Leu35del	conservative_inframe_deletion	1/28	ENST00000301873.11	NP_001123616.1
LTBP3	NM_021070.4	c.103_105delCTG	p.Leu35del	conservative_inframe_deletion	1/27		NP_066548.2
LTBP3	NM_001164266.1	c.-245_-243delCTG		5_prime_UTR_variant	1/27		NP_001157738.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LTBP3	ENST00000301873.11	c.103_105delCTG	p.Leu35del	conservative_inframe_deletion	1/28	2	NM_001130144.3	ENSP00000301873.5

Frequencies

GnomAD3 genomes AF: 0.00227 AC: 339 AN: 149054 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.00337

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000799

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000390

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.00156

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00254

Gnomad OTH AF: 0.000492

GnomAD3 exomes AF: 0.0652 AC: 2153 AN: 33030 Hom.: 1 AF XY: 0.0647 AC XY: 1240 AN XY: 19164

Gnomad AFR exome AF: 0.0830

Gnomad AMR exome AF: 0.0701

Gnomad ASJ exome AF: 0.0767

Gnomad EAS exome AF: 0.0818

Gnomad SAS exome AF: 0.0748

Gnomad FIN exome AF: 0.0612

Gnomad NFE exome AF: 0.0550

Gnomad OTH exome AF: 0.0537

GnomAD4 exome AF: 0.0180 AC: 19231 AN: 1071308 Hom.: 1 AF XY: 0.0184 AC XY: 9602 AN XY: 522796

Gnomad4 AFR exome AF: 0.0219

Gnomad4 AMR exome AF: 0.0383

Gnomad4 ASJ exome AF: 0.0238

Gnomad4 EAS exome AF: 0.0202

Gnomad4 SAS exome AF: 0.0332

Gnomad4 FIN exome AF: 0.0213

Gnomad4 NFE exome AF: 0.0164

Gnomad4 OTH exome AF: 0.0186

GnomAD4 genome AF: 0.00229 AC: 341 AN: 149142 Hom.: 0 Cov.: 27 AF XY: 0.00242 AC XY: 176 AN XY: 72768

Gnomad4 AFR AF: 0.00341

Gnomad4 AMR AF: 0.000798

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000392

Gnomad4 SAS AF: 0.000209

Gnomad4 FIN AF: 0.00156

Gnomad4 NFE AF: 0.00254

Gnomad4 OTH AF: 0.000487

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

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	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

Brachyolmia-amelogenesis imperfecta syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 22, 2024

- -

Brachyolmia-amelogenesis imperfecta syndrome;C4540511:Geleophysic dysplasia 3 Other:1

not provided, no classification provided

phenotyping only

GenomeConnect, ClinGen

-

Variant interpreted as Uncertain significance and reported on 02-29-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs71036212; hg19: chr11-65325325;