rs539110133

Variant names:

• chr11-65539063-GGGCGGCGTC-G
• rs539110133
• ENST00000528516.5:n.*3424_*3432delGACGCCGCC

Your query was ambiguous. Multiple possible variants found:

• chr11-65539063-GGGCGGCGTC-G
• chr11-65539063-GGGCGGCGTC-GGGCGGCGTCGGCGGCGTC
• chr11-65539063-GGGCGGCGTC-GGGCGGCGTCGGCGGCGTCGGCGGCGTC

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The ENST00000528516.5(LTBP3):​n.*3424_*3432delGACGCCGCC variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000551 in 1,364,696 control chromosomes in the GnomAD database, including 5 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00046 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00056 (4 hom.)
• Consequence: LTBP3 ENST00000528516.5 non_coding_transcript_exon
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.81
• Publications: 0 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 -4 ACMG points.

• BS2: High Homozygotes in GnomAdExome4 at 4 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTBP3	NM_001130144.3	c.*8_*16delGACGCCGCC		3_prime_UTR_variant	Exon 28 of 28	ENST00000301873.11	NP_001123616.1
LTBP3	NM_021070.4	c.*8_*16delGACGCCGCC		3_prime_UTR_variant	Exon 27 of 27		NP_066548.2
LTBP3	NM_001164266.1	c.*8_*16delGACGCCGCC		3_prime_UTR_variant	Exon 27 of 27		NP_001157738.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTBP3	ENST00000301873.11	c.*8_*16delGACGCCGCC		3_prime_UTR_variant	Exon 28 of 28	2	NM_001130144.3	ENSP00000301873.5

Frequencies

GnomAD3 genomes AF: 0.000461 AC: 70 AN: 152008 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000413

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000809

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000742 AC: 27 AN: 36384 AF XY: 0.000604

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00147

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00107

Gnomad OTH exome AF: 0.000936

GnomAD4 exome AF: 0.000562 AC: 682 AN: 1212688 Hom.: 4 AF XY: 0.000517 AC XY: 305 AN XY: 589414

African (AFR) AF: 0.000173 AC: 4 AN: 23068

American (AMR) AF: 0.000803 AC: 10 AN: 12450

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17208

East Asian (EAS) AF: 0.00 AC: 0 AN: 27340

South Asian (SAS) AF: 0.000226 AC: 13 AN: 57518

European-Finnish (FIN) AF: 0.0000671 AC: 2 AN: 29816

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3436

European-Non Finnish (NFE) AF: 0.000632 AC: 628 AN: 992990

Other (OTH) AF: 0.000512 AC: 25 AN: 48862

GnomAD4 genome AF: 0.000461 AC: 70 AN: 152008 Hom.: 1 Cov.: 33 AF XY: 0.000323 AC XY: 24 AN XY: 74262

African (AFR) AF: 0.000193 AC: 8 AN: 41414

American (AMR) AF: 0.000262 AC: 4 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5192

South Asian (SAS) AF: 0.000413 AC: 2 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10560

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000809 AC: 55 AN: 67968

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.000163 Hom.: 0

Bravo AF: 0.000446

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

LTBP3-related disorder Benign:1

Dec 16, 2020

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.8
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs539110133; hg19: chr11-65306534;