Variant rs147282006 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000428.3(LTBP2):c.1790-17G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0114 in 1,610,602 control chromosomes in the GnomAD database, including 136 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0084 ( 11 hom., cov: 33)

Exomes 𝑓: 0.012 ( 125 hom. )

Consequence

LTBP2
NM_000428.3 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.03

Variant links:

Genes affected

LTBP2 (HGNC:6715): (latent transforming growth factor beta binding protein 2) The protein encoded by this gene belongs to the family of latent transforming growth factor (TGF)-beta binding proteins (LTBP), which are extracellular matrix proteins with multi-domain structure. This protein is the largest member of the LTBP family possessing unique regions and with most similarity to the fibrillins. It has thus been suggested that it may have multiple functions: as a member of the TGF-beta latent complex, as a structural component of microfibrils, and a role in cell adhesion. [provided by RefSeq, Jul 2008]

LTBP2 links:

LTBP2 (HGNC:):

LTBP2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 14-74536017-C-T is Benign according to our data. Variant chr14-74536017-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 445676.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-74536017-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00843 (1283/152266) while in subpopulation NFE AF= 0.0132 (899/68008). AF 95% confidence interval is 0.0125. There are 11 homozygotes in gnomad4. There are 615 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LTBP2	NM_000428.3 linkuse as main transcript	c.1790-17G>A		intron_variant		ENST00000261978.9	NP_000419.1	Q14767

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
LTBP2	ENST00000261978.9 linkuse as main transcript	c.1790-17G>A	intron_variant	1	NM_000428.3	ENSP00000261978.4	Q14767
LTBP2	ENST00000556690.5 linkuse as main transcript	c.1790-17G>A	intron_variant	5		ENSP00000451477.1	G3V3X5
LTBP2	ENST00000553939.5 linkuse as main transcript	n.1790-17G>A	intron_variant	5		ENSP00000452110.1	G3V511
LTBP2	ENST00000557425.1 linkuse as main transcript	n.514-17G>A	intron_variant	2

Frequencies

GnomAD3 genomes

AF:

0.00844

AC:

1284

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00174

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00249

Gnomad ASJ

AF:

0.00749

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0221

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0132

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00925

AC:

2322

AN:

250988

Hom.:

AF XY:

0.00906

AC XY:

1230

AN XY:

135718

show subpopulations

Gnomad AFR exome

AF:

0.00197

Gnomad AMR exome

AF:

0.00281

Gnomad ASJ exome

AF:

0.00824

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.0248

Gnomad NFE exome

AF:

0.0134

Gnomad OTH exome

AF:

0.00800

GnomAD4 exome

AF:

0.0117

AC:

17121

AN:

1458336

Hom.:

125

Cov.:

AF XY:

0.0114

AC XY:

8239

AN XY:

725776

show subpopulations

Gnomad4 AFR exome

AF:

0.00141

Gnomad4 AMR exome

AF:

0.00268

Gnomad4 ASJ exome

AF:

0.00739

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.0264

Gnomad4 NFE exome

AF:

0.0134

Gnomad4 OTH exome

AF:

0.00873

GnomAD4 genome

AF:

0.00843

AC:

1283

AN:

152266

Hom.:

Cov.:

AF XY:

0.00826

AC XY:

615

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.00173

Gnomad4 AMR

AF:

0.00248

Gnomad4 ASJ

AF:

0.00749

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.0221

Gnomad4 NFE

AF:

0.0132

Gnomad4 OTH

AF:

0.00615

Alfa

AF:

0.0116

Hom.:

Bravo

AF:

0.00669

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jun 15, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.21

DANN

Benign

0.63

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