Variant chr2-32947681-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_206943.4(LTBP1):c.357C>A(p.His119Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000506 in 1,494,734 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00045 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00051 ( 0 hom. )

Consequence

LTBP1
NM_206943.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: -0.302

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.011304617).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LTBP1	NM_206943.4 linkuse as main transcript	c.357C>A	p.His119Gln	missense_variant	1/34	ENST00000404816.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LTBP1	ENST00000404816.7 linkuse as main transcript	c.357C>A	p.His119Gln	missense_variant	1/34	5	NM_206943.4	P3	Q14766-1

Frequencies

GnomAD3 genomes

AF:

0.000455

AC:

AN:

151736

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000479

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000854

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000399

AC:

AN:

115158

Hom.:

AF XY:

0.000304

AC XY:

AN XY:

65782

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000212

Gnomad NFE exome

AF:

0.000932

Gnomad OTH exome

AF:

0.000705

GnomAD4 exome

AF:

0.000512

AC:

687

AN:

1342890

Hom.:

Cov.:

AF XY:

0.000500

AC XY:

332

AN XY:

664298

show subpopulations

Gnomad4 AFR exome

AF:

0.0000732

Gnomad4 AMR exome

AF:

0.0000332

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000162

Gnomad4 FIN exome

AF:

0.000629

Gnomad4 NFE exome

AF:

0.000578

Gnomad4 OTH exome

AF:

0.000437

GnomAD4 genome

AF:

0.000454

AC:

AN:

151844

Hom.:

Cov.:

AF XY:

0.000377

AC XY:

AN XY:

74232

show subpopulations

Gnomad4 AFR

AF:

0.0000723

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000479

Gnomad4 NFE

AF:

0.000854

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000468

Hom.:

Bravo

AF:

0.000378

ExAC

AF:

0.000470

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 27, 2023

The c.357C>A (p.H119Q) alteration is located in exon 1 (coding exon 1) of the LTBP1 gene. This alteration results from a C to A substitution at nucleotide position 357, causing the histidine (H) at amino acid position 119 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.099

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.36

M_CAP

Pathogenic

0.50

MetaRNN

Benign

0.011

MetaSVM

Benign

-0.80

MutationAssessor

Benign

0.69

MutationTaster

Benign

0.94

N;N

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

0.41

REVEL

Benign

0.15

Sift

Benign

0.90

Sift4G

Benign

0.68

Vest4

0.14

MutPred

0.23

Gain of sheet (P = 0.1945);

MVP

0.093

MPC

0.13

ClinPred

0.020

GERP RS

1.3

Varity_R

0.062

gMVP

0.17

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

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