19-40598907-AATC-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The ENST00000308370.11(LTBP4):​c.147-288_147-286del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00543 in 152,216 control chromosomes in the GnomAD database, including 15 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0054 ( 15 hom., cov: 33)

Consequence

LTBP4
ENST00000308370.11 intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.975
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6
Variant 19-40598907-AATC-A is Benign according to our data. Variant chr19-40598907-AATC-A is described in ClinVar as [Likely_benign]. Clinvar id is 1219386.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00543 (827/152216) while in subpopulation AFR AF= 0.0177 (736/41522). AF 95% confidence interval is 0.0167. There are 15 homozygotes in gnomad4. There are 439 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LTBP4NM_001042544.1 linkuse as main transcriptc.147-288_147-286del intron_variant NP_001036009.1
LTBP4NM_003573.2 linkuse as main transcriptc.17-288_17-286del intron_variant NP_003564.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LTBP4ENST00000204005.13 linkuse as main transcriptc.17-288_17-286del intron_variant 1 ENSP00000204005 A2
LTBP4ENST00000308370.11 linkuse as main transcriptc.147-288_147-286del intron_variant 1 ENSP00000311905 A2Q8N2S1-1
LTBP4ENST00000594537.2 linkuse as main transcriptc.94+287_95-286del intron_variant, NMD_transcript_variant 5 ENSP00000480629

Frequencies

GnomAD3 genomes
AF:
0.00543
AC:
826
AN:
152098
Hom.:
15
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0178
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00419
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.000191
Gnomad OTH
AF:
0.00526
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.00543
AC:
827
AN:
152216
Hom.:
15
Cov.:
33
AF XY:
0.00590
AC XY:
439
AN XY:
74414
show subpopulations
Gnomad4 AFR
AF:
0.0177
Gnomad4 AMR
AF:
0.00418
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000191
Gnomad4 OTH
AF:
0.00521
Alfa
AF:
0.00548
Hom.:
0
Bravo
AF:
0.00618
Asia WGS
AF:
0.00202
AC:
8
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 submitterclinical testingGeneDxJul 21, 2020- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

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.

Other links and lift over

dbSNP: rs3071336; hg19: chr19-41104813; API