2-32947686-A-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_206943.4(LTBP1):c.362A>T(p.Asn121Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000017 in 1,349,666 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N121S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

LTBP1
NM_206943.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.22

Publications

1 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)

LTBP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.095639914).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_206943.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTBP1	NM_206943.4	MANE Select	c.362A>T	p.Asn121Ile	missense	Exon 1 of 34	NP_996826.3	Q14766-1
	LTBP1	NM_001394905.1		c.362A>T	p.Asn121Ile	missense	Exon 1 of 34	NP_001381834.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LTBP1	ENST00000404816.7	TSL:5 MANE Select	c.362A>T	p.Asn121Ile	missense	Exon 1 of 34	ENSP00000386043.2	Q14766-1
LTBP1	ENST00000929169.1		c.362A>T	p.Asn121Ile	missense	Exon 1 of 34	ENSP00000599228.1
LTBP1	ENST00000954823.1		c.362A>T	p.Asn121Ile	missense	Exon 1 of 34	ENSP00000624882.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

123342

AF XY:

0.00

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:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000170

AC:

AN:

1349666

Hom.:

Cov.:

AF XY:

0.0000210

AC XY:

AN XY:

668076

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27526

American (AMR)

AF:

0.00

AC:

AN:

31158

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23426

East Asian (EAS)

AF:

0.00

AC:

AN:

29358

South Asian (SAS)

AF:

0.00

AC:

AN:

74634

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46712

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5262

European-Non Finnish (NFE)

AF:

0.0000199

AC:

AN:

1056476

Other (OTH)

AF:

0.0000363

AC:

AN:

55114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.092

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.30

M_CAP

Pathogenic

0.36

MetaRNN

Benign

0.096

MetaSVM

Benign

-0.87

MutationAssessor

Benign

0.0

PhyloP100

1.2

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.55

REVEL

Benign

0.11

Sift

Benign

0.14

Sift4G

Benign

0.19

Vest4

0.32

MutPred

0.15

Loss of glycosylation at P126 (P = 0.1496)

MVP

0.12

MPC

0.16

ClinPred

0.14

GERP RS

2.2

Varity_R

0.088

gMVP

0.33

Mutation Taster

=98/2

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over