19-40596970-C-T

Position:

• chr19-40596970-C-T

Variant summary

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

The ENST00000204005.13(LTBP4):​c.17-2227C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 151,918 control chromosomes in the GnomAD database, including 2,610 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.18 (2610 hom., cov: 30)
• Consequence: LTBP4 ENST00000204005.13 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.575

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=-0.72).
• BP6: Variant 19-40596970-C-T is Benign according to our data. Variant chr19-40596970-C-T is described in ClinVar as [Benign]. Clinvar id is 668714.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LTBP4	NM_003573.2	c.17-2227C>T		intron_variant			NP_003564.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LTBP4	ENST00000204005.13	c.17-2227C>T		intron_variant		1		ENSP00000204005	A2
LTBP4	ENST00000599016.5	c.17-2227C>T		intron_variant, NMD_transcript_variant		3		ENSP00000482179
LTBP4	ENST00000600026.5	c.17-2227C>T		intron_variant, NMD_transcript_variant		3		ENSP00000483230

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27449 AN: 151796 Hom.: 2614 Cov.: 30

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.0945

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.179

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.181 AC: 27446 AN: 151918 Hom.: 2610 Cov.: 30 AF XY: 0.185 AC XY: 13722 AN XY: 74216

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.149

Gnomad4 ASJ AF: 0.210

Gnomad4 EAS AF: 0.277

Gnomad4 SAS AF: 0.258

Gnomad4 FIN AF: 0.249

Gnomad4 NFE AF: 0.174

Gnomad4 OTH AF: 0.177

Alfa AF: 0.187 Hom.: 333

Bravo AF: 0.173

Asia WGS AF: 0.235 AC: 817 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 19, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	8.3
DANN	Benign	0.91

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs73047963; hg19: chr19-41102876; COSMIC: COSV52582600; COSMIC: COSV52582600;