dbSNP rs6706122: LTBP1:c.1805-55C>A (chr2-33222025-C-A) – 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.1805-55C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0374 in 1,273,900 control chromosomes in the GnomAD database, including 2,231 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 ( 1022 hom., cov: 33)

Exomes 𝑓: 0.032 ( 1209 hom. )

Consequence

LTBP1
NM_206943.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.151

Publications

2 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=-0.82).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTBP1	NM_206943.4 link	c.1805-55C>A		intron_variant	Intron 8 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.1805-55C>A		intron_variant	Intron 8 of 33	5	NM_206943.4	ENSP00000386043.2		Q14766-1

Frequencies

GnomAD3 genomes

AF:

0.0776

AC:

11806

AN:

152070

Hom.:

1010

Cov.:

show subpopulations

Gnomad AFR

AF:

0.211

Gnomad AMI

AF:

0.0330

Gnomad AMR

AF:

0.0425

Gnomad ASJ

AF:

0.0565

Gnomad EAS

AF:

0.0266

Gnomad SAS

AF:

0.00746

Gnomad FIN

AF:

0.0170

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0249

Gnomad OTH

AF:

0.0746

GnomAD4 exome

AF:

0.0319

AC:

35805

AN:

1121712

Hom.:

1209

AF XY:

0.0302

AC XY:

17313

AN XY:

573634

show subpopulations

African (AFR)

AF:

0.223

AC:

6082

AN:

27262

American (AMR)

AF:

0.0251

AC:

1106

AN:

44078

Ashkenazi Jewish (ASJ)

AF:

0.0590

AC:

1412

AN:

23922

East Asian (EAS)

AF:

0.0436

AC:

1660

AN:

38046

South Asian (SAS)

AF:

0.00885

AC:

698

AN:

78840

European-Finnish (FIN)

AF:

0.0133

AC:

702

AN:

52782

Middle Eastern (MID)

AF:

0.0435

AC:

224

AN:

5144

European-Non Finnish (NFE)

AF:

0.0273

AC:

21896

AN:

802588

Other (OTH)

AF:

0.0413

AC:

2025

AN:

49050

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

1633

3267

4900

6534

8167

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

848

1696

2544

3392

4240

<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:

0.0779

AC:

11854

AN:

152188

Hom.:

1022

Cov.:

AF XY:

0.0750

AC XY:

5580

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.211

AC:

8758

AN:

41474

American (AMR)

AF:

0.0425

AC:

650

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0565

AC:

196

AN:

3470

East Asian (EAS)

AF:

0.0266

AC:

138

AN:

5182

South Asian (SAS)

AF:

0.00767

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0170

AC:

180

AN:

10610

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0249

AC:

1691

AN:

68016

Other (OTH)

AF:

0.0734

AC:

155

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

525

1051

1576

2102

2627

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

224

336

448

560

<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:

0.0423

Hom.:

891

Bravo

AF:

0.0864

Asia WGS

AF:

0.0340

AC:

119

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

3.3

(source)

DANN

Benign

0.25

PhyloP100

-0.15

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