Genetic Variant LTBP3:n.*3424_*3432dupGACGCCGCC (chr11-65539063-G-GGGCGGCGTC) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

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

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.174

Publications

0 publications found

Variant links:

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

LTBP3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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	Effect	Exon rank	MANE	Protein	UniProt
LTBP3	NM_001130144.3 link	c.8_16dupGACGCCGCC	3_prime_UTR_variant	Exon 28 of 28	ENST00000301873.11	NP_001123616.1	Q9NS15-1Q8WYU6
LTBP3	NM_021070.4 link	c.8_16dupGACGCCGCC	3_prime_UTR_variant	Exon 27 of 27		NP_066548.2	Q9NS15-2Q8WYU6
LTBP3	NM_001164266.1 link	c.8_16dupGACGCCGCC	3_prime_UTR_variant	Exon 27 of 27		NP_001157738.1	Q9NS15B9EG76Q8WYU6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTBP3	ENST00000301873.11 link	c.8_16dupGACGCCGCC		3_prime_UTR_variant	Exon 28 of 28	2	NM_001130144.3	ENSP00000301873.5		Q9NS15-1

Frequencies

GnomAD3 genomes

AF:

0.00268

AC:

408

AN:

152002

Hom.:

Cov.:

show subpopulations

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:

AN:

36384

AF XY:

0.000325

show subpopulations

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.:

Cov.:

AF XY:

0.00271

AC XY:

1599

AN XY:

589236

show subpopulations

African (AFR)

AF:

0.000737

AC:

AN:

23062

American (AMR)

AF:

0.000964

AC:

AN:

12446

Ashkenazi Jewish (ASJ)

AF:

0.00372

AC:

AN:

17190

East Asian (EAS)

AF:

0.00154

AC:

AN:

27326

South Asian (SAS)

AF:

0.00139

AC:

AN:

57466

European-Finnish (FIN)

AF:

0.000738

AC:

AN:

29812

Middle Eastern (MID)

AF:

0.000582

AC:

AN:

3434

European-Non Finnish (NFE)

AF:

0.00313

AC:

3106

AN:

992778

Other (OTH)

AF:

0.00250

AC:

122

AN:

48854

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

175

349

524

698

873

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00268

AC:

408

AN:

152112

Hom.:

Cov.:

AF XY:

0.00266

AC XY:

198

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.00137

AC:

AN:

41534

American (AMR)

AF:

0.00223

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00749

AC:

AN:

3472

East Asian (EAS)

AF:

0.00232

AC:

AN:

5176

South Asian (SAS)

AF:

0.00393

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.000284

AC:

AN:

10560

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00363

AC:

247

AN:

67952

Other (OTH)

AF:

0.00427

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

106

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000597

Hom.:

Asia WGS

AF:

0.00260

AC:

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

(source)

Splicing

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

Publications

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chr11-65539063-G-GGGCGGCGTC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over