11-65539063-GGGCGGCGTC-GGGCGGCGTCGGCGGCGTC

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The ENST00000528516.5(LTBP3):​n.*3424_*3432dupGACGCCGCC 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 0.00284 in 1,364,480 control chromosomes in the GnomAD database, including 6 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0027 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0029 (6 hom.)
• Consequence: LTBP3 ENST00000528516.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.174
• 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: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00268 (408/152112) while in subpopulation SAS AF = 0.00393 (19/4834). AF 95% confidence interval is 0.00326. There are 0 homozygotes in GnomAd4. There are 198 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 6 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTBP3	NM_001130144.3	c.*8_*16dupGACGCCGCC		3_prime_UTR_variant	Exon 28 of 28	ENST00000301873.11	NP_001123616.1
LTBP3	NM_021070.4	c.*8_*16dupGACGCCGCC		3_prime_UTR_variant	Exon 27 of 27		NP_066548.2
LTBP3	NM_001164266.1	c.*8_*16dupGACGCCGCC		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_*16dupGACGCCGCC		3_prime_UTR_variant	Exon 28 of 28	2	NM_001130144.3	ENSP00000301873.5

Frequencies

GnomAD3 genomes AF: 0.00268 AC: 408 AN: 152002 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00138

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00223

Gnomad ASJ AF: 0.00749

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.00393

Gnomad FIN AF: 0.000284

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00363

Gnomad OTH AF: 0.00431

GnomAD2 exomes AF: 0.000302 AC: 11 AN: 36384 AF XY: 0.000325

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000402

Gnomad NFE exome AF: 0.000509

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00286 AC: 3467 AN: 1212368 Hom.: 6 Cov.: 31 AF XY: 0.00271 AC XY: 1599 AN XY: 589236

African (AFR) AF: 0.000737 AC: 17 AN: 23062

American (AMR) AF: 0.000964 AC: 12 AN: 12446

Ashkenazi Jewish (ASJ) AF: 0.00372 AC: 64 AN: 17190

East Asian (EAS) AF: 0.00154 AC: 42 AN: 27326

South Asian (SAS) AF: 0.00139 AC: 80 AN: 57466

European-Finnish (FIN) AF: 0.000738 AC: 22 AN: 29812

Middle Eastern (MID) AF: 0.000582 AC: 2 AN: 3434

European-Non Finnish (NFE) AF: 0.00313 AC: 3106 AN: 992778

Other (OTH) AF: 0.00250 AC: 122 AN: 48854

GnomAD4 genome AF: 0.00268 AC: 408 AN: 152112 Hom.: 0 Cov.: 33 AF XY: 0.00266 AC XY: 198 AN XY: 74378

African (AFR) AF: 0.00137 AC: 57 AN: 41534

American (AMR) AF: 0.00223 AC: 34 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00749 AC: 26 AN: 3472

East Asian (EAS) AF: 0.00232 AC: 12 AN: 5176

South Asian (SAS) AF: 0.00393 AC: 19 AN: 4834

European-Finnish (FIN) AF: 0.000284 AC: 3 AN: 10560

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.00363 AC: 247 AN: 67952

Other (OTH) AF: 0.00427 AC: 9 AN: 2110

Alfa AF: 0.000597 Hom.: 0

Asia WGS AF: 0.00260 AC: 9 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.17
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;