11-65557854-CCAGCAGCAGCAGCAGCAGCAG-CCAGCAGCAG

Variant names:

• chr11-65557854-CCAGCAGCAGCAG-C
• rs71036212
• NM_001130144.3:c.94_105delCTGCTGCTGCTG

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_001130144.3(LTBP3):​c.94_105delCTGCTGCTGCTG​(p.Leu32_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 0.0000295 in 1,320,176 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 27)
  • Exomes 𝑓: 0.000031 (0 hom.)
• Consequence: LTBP3 NM_001130144.3 conservative_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 0.773
• Publications: 4 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001130144.3

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130144.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTBP3	NM_001130144.3	MANE Select	c.94_105delCTGCTGCTGCTG	p.Leu32_Leu35del	conservative_inframe_deletion	Exon 1 of 28	NP_001123616.1
	LTBP3	NM_021070.4		c.94_105delCTGCTGCTGCTG	p.Leu32_Leu35del	conservative_inframe_deletion	Exon 1 of 27	NP_066548.2
	LTBP3	NM_001164266.1		c.-254_-243delCTGCTGCTGCTG		5_prime_UTR	Exon 1 of 27	NP_001157738.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTBP3	ENST00000301873.11	TSL:2 MANE Select	c.94_105delCTGCTGCTGCTG	p.Leu32_Leu35del	conservative_inframe_deletion	Exon 1 of 28	ENSP00000301873.5
	LTBP3	ENST00000322147.8	TSL:1	c.94_105delCTGCTGCTGCTG	p.Leu32_Leu35del	conservative_inframe_deletion	Exon 1 of 27	ENSP00000326647.4
	LTBP3	ENST00000528516.5	TSL:1	n.94_105delCTGCTGCTGCTG		non_coding_transcript_exon	Exon 1 of 27	ENSP00000432350.1

Frequencies

GnomAD3 genomes AF: 0.0000201 AC: 3 AN: 149160 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.0000244

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000299

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000307 AC: 36 AN: 1171016 Hom.: 0 AF XY: 0.0000350 AC XY: 20 AN XY: 572178

African (AFR) AF: 0.0000836 AC: 2 AN: 23930

American (AMR) AF: 0.00 AC: 0 AN: 19204

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17698

East Asian (EAS) AF: 0.00 AC: 0 AN: 25428

South Asian (SAS) AF: 0.000104 AC: 5 AN: 48002

European-Finnish (FIN) AF: 0.000113 AC: 3 AN: 26432

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3822

European-Non Finnish (NFE) AF: 0.0000261 AC: 25 AN: 959624

Other (OTH) AF: 0.0000213 AC: 1 AN: 46876

GnomAD4 genome AF: 0.0000201 AC: 3 AN: 149160 Hom.: 0 Cov.: 27 AF XY: 0.0000137 AC XY: 1 AN XY: 72742

African (AFR) AF: 0.0000244 AC: 1 AN: 40926

American (AMR) AF: 0.00 AC: 0 AN: 15028

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3424

East Asian (EAS) AF: 0.00 AC: 0 AN: 5124

South Asian (SAS) AF: 0.00 AC: 0 AN: 4788

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9686

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 308

European-Non Finnish (NFE) AF: 0.0000299 AC: 2 AN: 66932

Other (OTH) AF: 0.00 AC: 0 AN: 2036

Alfa AF: 0.00 Hom.: 40

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Brachyolmia-amelogenesis imperfecta syndrome (1)
-	1	-	Brachyolmia-amelogenesis imperfecta syndrome;C4540511:Geleophysic dysplasia 3 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.77
Mutation Taster		=185/15	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs71036212; hg19: chr11-65325325;