Variant chr19-40599071-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000308370.11(LTBP4):c.147-126C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 853,032 control chromosomes in the GnomAD database, including 16,749 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 2637 hom., cov: 31)

Exomes 𝑓: 0.20 ( 14112 hom. )

Consequence

LTBP4
ENST00000308370.11 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.499

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 19-40599071-C-T is Benign according to our data. Variant chr19-40599071-C-T is described in ClinVar as [Benign]. Clinvar id is 1226027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LTBP4	NM_001042544.1 linkuse as main transcript	c.147-126C>T		intron_variant
LTBP4	NM_003573.2 linkuse as main transcript	c.17-126C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	Appris	UniProt
LTBP4	ENST00000204005.13 linkuse as main transcript	c.17-126C>T	intron_variant	1	A2
LTBP4	ENST00000308370.11 linkuse as main transcript	c.147-126C>T	intron_variant	1	A2	Q8N2S1-1
LTBP4	ENST00000594537.2 linkuse as main transcript	c.95-126C>T	intron_variant, NMD_transcript_variant	5

Frequencies

GnomAD3 genomes

AF:

0.181

AC:

27477

AN:

151948

Hom.:

2642

Cov.:

show subpopulations

Gnomad AFR

AF:

0.158

Gnomad AMI

AF:

0.0943

Gnomad AMR

AF:

0.148

Gnomad ASJ

AF:

0.220

Gnomad EAS

AF:

0.279

Gnomad SAS

AF:

0.274

Gnomad FIN

AF:

0.250

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.176

Gnomad OTH

AF:

0.177

GnomAD4 exome

AF:

0.195

AC:

136770

AN:

700964

Hom.:

14112

AF XY:

0.201

AC XY:

74315

AN XY:

369292

show subpopulations

Gnomad4 AFR exome

AF:

0.156

Gnomad4 AMR exome

AF:

0.132

Gnomad4 ASJ exome

AF:

0.208

Gnomad4 EAS exome

AF:

0.261

Gnomad4 SAS exome

AF:

0.287

Gnomad4 FIN exome

AF:

0.233

Gnomad4 NFE exome

AF:

0.178

Gnomad4 OTH exome

AF:

0.199

GnomAD4 genome

AF:

0.181

AC:

27468

AN:

152068

Hom.:

2637

Cov.:

AF XY:

0.185

AC XY:

13752

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.158

Gnomad4 AMR

AF:

0.147

Gnomad4 ASJ

AF:

0.220

Gnomad4 EAS

AF:

0.279

Gnomad4 SAS

AF:

0.274

Gnomad4 FIN

AF:

0.250

Gnomad4 NFE

AF:

0.176

Gnomad4 OTH

AF:

0.175

Alfa

AF:

0.182

Hom.:

588

Bravo

AF:

0.172

Asia WGS

AF:

0.240

AC:

834

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.91

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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