Variant 19-40597416-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000308370.11(LTBP4):c.146+36A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000606 in 1,478,074 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0034 ( 5 hom., cov: 30)

Exomes 𝑓: 0.00028 ( 5 hom. )

Consequence

LTBP4
ENST00000308370.11 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.45

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 Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 19-40597416-A-G is Benign according to our data. Variant chr19-40597416-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1178562.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00341 (519/152126) while in subpopulation AFR AF= 0.0122 (506/41500). AF 95% confidence interval is 0.0113. There are 5 homozygotes in gnomad4. There are 268 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LTBP4	NM_001042544.1 linkuse as main transcript	c.146+36A>G		intron_variant
LTBP4	NM_003573.2 linkuse as main transcript	c.17-1781A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	Appris	UniProt
LTBP4	ENST00000204005.13 linkuse as main transcript	c.17-1781A>G	intron_variant	1	A2
LTBP4	ENST00000308370.11 linkuse as main transcript	c.146+36A>G	intron_variant	1	A2	Q8N2S1-1
LTBP4	ENST00000599016.5 linkuse as main transcript	c.17-1781A>G	intron_variant, NMD_transcript_variant	3
LTBP4	ENST00000600026.5 linkuse as main transcript	c.17-1781A>G	intron_variant, NMD_transcript_variant	3

Frequencies

GnomAD3 genomes

AF:

0.00341

AC:

518

AN:

152014

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0122

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

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:

0.0000294

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.000373

AC:

AN:

91162

Hom.:

AF XY:

0.000214

AC XY:

AN XY:

51384

show subpopulations

Gnomad AFR exome

AF:

0.0127

Gnomad AMR exome

AF:

0.000296

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:

0.0000279

Gnomad OTH exome

AF:

0.000377

GnomAD4 exome

AF:

0.000284

AC:

377

AN:

1325948

Hom.:

Cov.:

AF XY:

0.000250

AC XY:

163

AN XY:

651570

show subpopulations

Gnomad4 AFR exome

AF:

0.0116

Gnomad4 AMR exome

AF:

0.000347

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000271

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000115

Gnomad4 OTH exome

AF:

0.000653

GnomAD4 genome

AF:

0.00341

AC:

519

AN:

152126

Hom.:

Cov.:

AF XY:

0.00360

AC XY:

268

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.0122

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000475

Alfa

AF:

0.00262

Hom.:

Bravo

AF:

0.00449

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 20, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.2

DANN

Benign

0.41

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over