dbSNP rs2290447: LTBP1:c.1202-57A>G (chr2-33186799-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_206943.4(LTBP1):c.1202-57A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0364 in 1,360,332 control chromosomes in the GnomAD database, including 2,232 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.078 ( 1000 hom., cov: 32)

Exomes 𝑓: 0.031 ( 1232 hom. )

Consequence

LTBP1
NM_206943.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0320

Publications

4 publications found

Variant links:

Genes affected

LTBP1 (HGNC:6714): (latent transforming growth factor beta binding protein 1) The protein encoded by this gene belongs to the family of latent TGF-beta binding proteins (LTBPs). The secretion and activation of TGF-betas is regulated by their association with latency-associated proteins and with latent TGF-beta binding proteins. The product of this gene targets latent complexes of transforming growth factor beta to the extracellular matrix, where the latent cytokine is subsequently activated by several different mechanisms. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

LTBP1 Gene-Disease associations (from GenCC):

cutis laxa, autosomal recessive, type 2E
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

LTBP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTBP1	NM_206943.4 link	c.1202-57A>G		intron_variant	Intron 5 of 33	ENST00000404816.7	NP_996826.3	Q14766-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTBP1	ENST00000404816.7 link	c.1202-57A>G		intron_variant	Intron 5 of 33	5	NM_206943.4	ENSP00000386043.2		Q14766-1

Frequencies

GnomAD3 genomes

AF:

0.0781

AC:

11872

AN:

152082

Hom.:

986

Cov.:

show subpopulations

Gnomad AFR

AF:

0.212

Gnomad AMI

AF:

0.0340

Gnomad AMR

AF:

0.0443

Gnomad ASJ

AF:

0.0573

Gnomad EAS

AF:

0.0271

Gnomad SAS

AF:

0.00726

Gnomad FIN

AF:

0.0170

Gnomad MID

AF:

0.0764

Gnomad NFE

AF:

0.0248

Gnomad OTH

AF:

0.0655

GnomAD4 exome

AF:

0.0312

AC:

37660

AN:

1208132

Hom.:

1232

AF XY:

0.0296

AC XY:

17997

AN XY:

608960

show subpopulations

African (AFR)

AF:

0.218

AC:

6242

AN:

28598

American (AMR)

AF:

0.0257

AC:

1049

AN:

40850

Ashkenazi Jewish (ASJ)

AF:

0.0591

AC:

1390

AN:

23514

East Asian (EAS)

AF:

0.0441

AC:

1686

AN:

38244

South Asian (SAS)

AF:

0.00922

AC:

713

AN:

77300

European-Finnish (FIN)

AF:

0.0132

AC:

684

AN:

51954

Middle Eastern (MID)

AF:

0.0367

AC:

193

AN:

5262

European-Non Finnish (NFE)

AF:

0.0265

AC:

23585

AN:

890462

Other (OTH)

AF:

0.0408

AC:

2118

AN:

51948

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

1812

3625

5437

7250

9062

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

960

1920

2880

3840

4800

<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:

0.0783

AC:

11911

AN:

152200

Hom.:

1000

Cov.:

AF XY:

0.0750

AC XY:

5581

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.212

AC:

8808

AN:

41496

American (AMR)

AF:

0.0442

AC:

676

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0573

AC:

199

AN:

3472

East Asian (EAS)

AF:

0.0272

AC:

141

AN:

5188

South Asian (SAS)

AF:

0.00748

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.0170

AC:

180

AN:

10610

Middle Eastern (MID)

AF:

0.0616

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0248

AC:

1686

AN:

68008

Other (OTH)

AF:

0.0643

AC:

136

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

510

1020

1530

2040

2550

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

240

360

480

600

<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:

0.0624

Hom.:

111

Bravo

AF:

0.0878

Asia WGS

AF:

0.0330

AC:

115

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

3.3

(source)

DANN

Benign

0.48

PhyloP100

0.032

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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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