19-40599071-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.499

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	c.147-126C>T		intron_variant
LTBP4	NM_003573.2	c.17-126C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LTBP4	ENST00000204005.13	c.17-126C>T		intron_variant		1		A2
LTBP4	ENST00000308370.11	c.147-126C>T		intron_variant		1		A2
LTBP4	ENST00000594537.2	c.95-126C>T		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27477 AN: 151948 Hom.: 2642 Cov.: 31

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

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.: 31 AF XY: 0.185 AC XY: 13752 AN XY: 74342

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
Cadd	Benign	11
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

Other links and lift over

dbSNP: rs55815263; hg19: chr19-41104977; COSMIC: COSV52593103; COSMIC: COSV52593103;