Genetic Variant LTBP3:c.*8_*16delGACGCCGCC (chr11-65539063-GGGCGGCGTC-G) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP6BS2

The NM_001130144.3(LTBP3):c.*8_*16delGACGCCGCC variant causes a 3 prime UTR 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. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00046 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00056 ( 4 hom. )

Consequence

LTBP3
NM_001130144.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.81

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 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP6

Variant 11-65539063-GGGCGGCGTC-G is Benign according to our data. Variant chr11-65539063-GGGCGGCGTC-G is described in ClinVar as [Likely_benign]. Clinvar id is 3043750.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 4 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
LTBP3	NM_001130144.3 link	c.8_16delGACGCCGCC	3_prime_UTR_variant	Exon 28 of 28	ENST00000301873.11	NP_001123616.1	Q9NS15-1Q8WYU6
LTBP3	NM_021070.4 link	c.8_16delGACGCCGCC	3_prime_UTR_variant	Exon 27 of 27		NP_066548.2	Q9NS15-2Q8WYU6
LTBP3	NM_001164266.1 link	c.8_16delGACGCCGCC	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 link	c.8_16delGACGCCGCC		3_prime_UTR_variant	Exon 28 of 28	2	NM_001130144.3	ENSP00000301873.5		Q9NS15-1

Frequencies

GnomAD3 genomes

AF:

0.000461

AC:

AN:

152008

Hom.:

Cov.:

show subpopulations

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:

AN:

36384

AF XY:

0.000604

show subpopulations

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.:

AF XY:

0.000517

AC XY:

305

AN XY:

589414

show subpopulations

Gnomad4 AFR exome

AF:

0.000173

AC:

AN:

23068

Gnomad4 AMR exome

AF:

0.000803

AC:

AN:

12450

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

17208

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

27340

Gnomad4 SAS exome

AF:

0.000226

AC:

AN:

57518

Gnomad4 FIN exome

AF:

0.0000671

AC:

AN:

29816

Gnomad4 NFE exome

AF:

0.000632

AC:

628

AN:

992990

Gnomad4 Remaining exome

AF:

0.000512

AC:

AN:

48862

Heterozygous variant carriers

101

135

169

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Variant carriers

110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000461

AC:

AN:

152008

Hom.:

Cov.:

AF XY:

0.000323

AC XY:

AN XY:

74262

show subpopulations

Gnomad4 AFR

AF:

0.000193

AC:

0.000193171

AN:

0.000193171

Gnomad4 AMR

AF:

0.000262

AC:

0.000262295

AN:

0.000262295

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.000193

AC:

0.000192604

AN:

0.000192604

Gnomad4 SAS

AF:

0.000413

AC:

0.000413394

AN:

0.000413394

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.000809

AC:

0.000809204

AN:

0.000809204

Gnomad4 OTH

AF:

0.00

AC:

AN:

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000163

Hom.:

Bravo

AF:

0.000446

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

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

Mutation Taster

=100/0

polymorphism

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over