19-40598954-G-T

Position:

• chr19-40598954-G-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.147-243G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 151,990 control chromosomes in the GnomAD database, including 21,000 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.50 (21000 hom., cov: 32)
• Consequence: LTBP4 ENST00000308370.11 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.227

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=-0.96).
• BP6: Variant 19-40598954-G-T is Benign according to our data. Variant chr19-40598954-G-T is described in ClinVar as [Benign]. Clinvar id is 1286634.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LTBP4	NM_001042544.1	c.147-243G>T		intron_variant			NP_001036009.1
LTBP4	NM_003573.2	c.17-243G>T		intron_variant			NP_003564.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LTBP4	ENST00000204005.13	c.17-243G>T		intron_variant		1		ENSP00000204005	A2
LTBP4	ENST00000308370.11	c.147-243G>T		intron_variant		1		ENSP00000311905	A2
LTBP4	ENST00000594537.2	c.95-243G>T		intron_variant, NMD_transcript_variant		5		ENSP00000480629

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76164 AN: 151872 Hom.: 20962 Cov.: 32

Gnomad AFR AF: 0.739

Gnomad AMI AF: 0.358

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.557

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.472

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

GnomAD4 genome AF: 0.502 AC: 76260 AN: 151990 Hom.: 21000 Cov.: 32 AF XY: 0.503 AC XY: 37375 AN XY: 74292

Gnomad4 AFR AF: 0.740

Gnomad4 AMR AF: 0.383

Gnomad4 ASJ AF: 0.557

Gnomad4 EAS AF: 0.398

Gnomad4 SAS AF: 0.536

Gnomad4 FIN AF: 0.465

Gnomad4 NFE AF: 0.394

Gnomad4 OTH AF: 0.471

Alfa AF: 0.416 Hom.: 13526

Bravo AF: 0.504

Asia WGS AF: 0.492 AC: 1709 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 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	6.6
DANN	Benign	0.31

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

Other links and lift over

dbSNP: rs1864074; hg19: chr19-41104860;