Variant 19-40597256-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000308370.11(LTBP4):c.22G>T(p.Gly8Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000444 in 1,508,274 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000046 ( 0 hom. )

Consequence

LTBP4
ENST00000308370.11 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.119

Variant links:

Genes affected

LTBP4 (HGNC:6717): (latent transforming growth factor beta binding protein 4) The protein encoded by this gene binds transforming growth factor beta (TGFB) as it is secreted and targeted to the extracellular matrix. TGFB is biologically latent after secretion and insertion into the extracellular matrix, and sheds TGFB and other proteins upon activation. Defects in this gene may be a cause of cutis laxa and severe pulmonary, gastrointestinal, and urinary abnormalities. Three transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, May 2010]

LTBP4 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.076741725).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LTBP4	NM_001042544.1 linkuse as main transcript	c.22G>T	p.Gly8Cys	missense_variant	1/33
LTBP4	NM_003573.2 linkuse as main transcript	c.17-1941G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Appris	UniProt
LTBP4	ENST00000308370.11 linkuse as main transcript	c.22G>T	p.Gly8Cys	missense_variant	1/33	1	A2	Q8N2S1-1
LTBP4	ENST00000204005.13 linkuse as main transcript	c.17-1941G>T		intron_variant		1	A2
LTBP4	ENST00000599016.5 linkuse as main transcript	c.17-1941G>T		intron_variant, NMD_transcript_variant		3
LTBP4	ENST00000600026.5 linkuse as main transcript	c.17-1941G>T		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000949

AC:

AN:

105358

Hom.:

AF XY:

0.00

AC XY:

AN XY:

58836

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:

0.00

Gnomad NFE exome

AF:

0.0000258

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000465

AC:

AN:

1356188

Hom.:

Cov.:

AF XY:

0.0000508

AC XY:

AN XY:

668676

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000581

Gnomad4 OTH exome

AF:

0.0000177

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152086

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000174

Hom.:

Bravo

AF:

0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.089

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.40

M_CAP

Pathogenic

0.39

MetaRNN

Benign

0.077

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.34

MutationTaster

Benign

1.0

D;N

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.49

REVEL

Uncertain

0.30

Sift

Pathogenic

0.0

Sift4G

Benign

0.15

Polyphen

0.0010

Vest4

0.12

MutPred

0.17

Loss of relative solvent accessibility (P = 0.0414);

MVP

0.26

MPC

0.87

ClinPred

0.21

GERP RS

-1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

Varity_R

0.23

gMVP

0.32

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