Variant rs2290427 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_206943.4(LTBP1):c.3026C>A(p.Pro1009Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0203 in 1,613,984 control chromosomes in the GnomAD database, including 407 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.015 ( 21 hom., cov: 32)

Exomes 𝑓: 0.021 ( 386 hom. )

Consequence

LTBP1
NM_206943.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.43

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:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008792281).

BP6

Variant 2-33280072-C-A is Benign according to our data. Variant chr2-33280072-C-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0145 (2212/152240) while in subpopulation EAS AF= 0.0253 (131/5186). AF 95% confidence interval is 0.0217. There are 21 homozygotes in gnomad4. There are 1018 alleles in male gnomad4 subpopulation. This position pass quality control queck.

BS2

High Homozygotes in GnomAd at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LTBP1	NM_206943.4 linkuse as main transcript	c.3026C>A	p.Pro1009Gln	missense_variant	19/34	ENST00000404816.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LTBP1	ENST00000404816.7 linkuse as main transcript	c.3026C>A	p.Pro1009Gln	missense_variant	19/34	5	NM_206943.4	P3	Q14766-1
	ENST00000650179.1 linkuse as main transcript	n.227+853G>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0145

AC:

2213

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00403

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0147

Gnomad ASJ

AF:

0.0161

Gnomad EAS

AF:

0.0252

Gnomad SAS

AF:

0.00560

Gnomad FIN

AF:

0.0163

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0205

Gnomad OTH

AF:

0.0163

GnomAD3 exomes

AF:

0.0154

AC:

3877

AN:

251246

Hom.:

AF XY:

0.0154

AC XY:

2090

AN XY:

135768

show subpopulations

Gnomad AFR exome

AF:

0.00400

Gnomad AMR exome

AF:

0.00844

Gnomad ASJ exome

AF:

0.0189

Gnomad EAS exome

AF:

0.0237

Gnomad SAS exome

AF:

0.00553

Gnomad FIN exome

AF:

0.0136

Gnomad NFE exome

AF:

0.0206

Gnomad OTH exome

AF:

0.0144

GnomAD4 exome

AF:

0.0209

AC:

30613

AN:

1461744

Hom.:

386

Cov.:

AF XY:

0.0203

AC XY:

14750

AN XY:

727168

show subpopulations

Gnomad4 AFR exome

AF:

0.00388

Gnomad4 AMR exome

AF:

0.00865

Gnomad4 ASJ exome

AF:

0.0198

Gnomad4 EAS exome

AF:

0.0400

Gnomad4 SAS exome

AF:

0.00605

Gnomad4 FIN exome

AF:

0.0132

Gnomad4 NFE exome

AF:

0.0230

Gnomad4 OTH exome

AF:

0.0183

GnomAD4 genome

AF:

0.0145

AC:

2212

AN:

152240

Hom.:

Cov.:

AF XY:

0.0137

AC XY:

1018

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.00402

Gnomad4 AMR

AF:

0.0147

Gnomad4 ASJ

AF:

0.0161

Gnomad4 EAS

AF:

0.0253

Gnomad4 SAS

AF:

0.00560

Gnomad4 FIN

AF:

0.0163

Gnomad4 NFE

AF:

0.0205

Gnomad4 OTH

AF:

0.0156

Alfa

AF:

0.0191

Hom.:

Bravo

AF:

0.0137

TwinsUK

AF:

0.0240

AC:

ALSPAC

AF:

0.0259

AC:

100

ESP6500AA

AF:

0.00545

AC:

ESP6500EA

AF:

0.0209

AC:

180

ExAC

AF:

0.0152

AC:

1850

Asia WGS

AF:

0.0100

AC:

AN:

3478

EpiCase

AF:

0.0194

EpiControl

AF:

0.0191

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Uncertain

-0.010

Cadd

Pathogenic

Dann

Uncertain

0.99

DEOGEN2

Uncertain

0.68

D;.;D;.;.

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.81

T;T;T;T;T

MetaRNN

Benign

0.0088

T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.4

L;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D

PrimateAI

Uncertain

0.55

PROVEAN

Pathogenic

-6.7

D;D;D;D;D

REVEL

Pathogenic

0.68

Sift

Uncertain

0.0020

D;D;D;D;D

Sift4G

Uncertain

0.0020

D;D;D;D;D

Polyphen

1.0

D;D;.;D;D

Vest4

0.67

MPC

0.57

ClinPred

0.031

GERP RS

5.5

Varity_R

0.54

gMVP

0.77

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over