11-65557854-CCAGCAGCAGCAGCAGCAGCAG-CCAGCAG

Variant names:

• chr11-65557854-CCAGCAGCAGCAGCAG-C
• rs71036212
• NM_001130144.3:c.91_105delCTGCTGCTGCTGCTG

Variant summary

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

The NM_001130144.3(LTBP3):​c.91_105delCTGCTGCTGCTGCTG​(p.Leu31_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 0.0000485 in 1,320,328 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 0.00010 (0 hom., cov: 27)
  • Exomes 𝑓: 0.000042 (0 hom.)
• Consequence: LTBP3 NM_001130144.3 conservative_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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.91_105delCTGCTGCTGCTGCTG	p.Leu31_Leu35del	conservative_inframe_deletion	Exon 1 of 28	NP_001123616.1
	LTBP3	NM_021070.4		c.91_105delCTGCTGCTGCTGCTG	p.Leu31_Leu35del	conservative_inframe_deletion	Exon 1 of 27	NP_066548.2
	LTBP3	NM_001164266.1		c.-257_-243delCTGCTGCTGCTGCTG		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.91_105delCTGCTGCTGCTGCTG	p.Leu31_Leu35del	conservative_inframe_deletion	Exon 1 of 28	ENSP00000301873.5
	LTBP3	ENST00000322147.8	TSL:1	c.91_105delCTGCTGCTGCTGCTG	p.Leu31_Leu35del	conservative_inframe_deletion	Exon 1 of 27	ENSP00000326647.4
	LTBP3	ENST00000528516.5	TSL:1	n.91_105delCTGCTGCTGCTGCTG		non_coding_transcript_exon	Exon 1 of 27	ENSP00000432350.1

Frequencies

GnomAD3 genomes AF: 0.000101 AC: 15 AN: 149162 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.0000489

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000665

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.000103

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000134

Gnomad OTH AF: 0.000491

GnomAD4 exome AF: 0.0000418 AC: 49 AN: 1171076 Hom.: 0 AF XY: 0.0000437 AC XY: 25 AN XY: 572202

African (AFR) AF: 0.0000417 AC: 1 AN: 23982

American (AMR) AF: 0.000104 AC: 2 AN: 19204

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 25430

South Asian (SAS) AF: 0.0000833 AC: 4 AN: 48006

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26432

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

European-Non Finnish (NFE) AF: 0.0000427 AC: 41 AN: 959624

Other (OTH) AF: 0.0000213 AC: 1 AN: 46878

GnomAD4 genome AF: 0.000101 AC: 15 AN: 149252 Hom.: 0 Cov.: 27 AF XY: 0.000110 AC XY: 8 AN XY: 72844

African (AFR) AF: 0.0000487 AC: 2 AN: 41032

American (AMR) AF: 0.0000665 AC: 1 AN: 15046

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5110

South Asian (SAS) AF: 0.000209 AC: 1 AN: 4782

European-Finnish (FIN) AF: 0.000103 AC: 1 AN: 9686

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 286

European-Non Finnish (NFE) AF: 0.000134 AC: 9 AN: 66922

Other (OTH) AF: 0.000486 AC: 1 AN: 2056

Alfa AF: 0.00 Hom.: 40

Bravo AF: 0.0000718

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Brachyolmia-amelogenesis imperfecta syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.77
Mutation Taster		=153/47	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;