Variant 14-74499066-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000428.3(LTBP2):c.*1818C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 217,940 control chromosomes in the GnomAD database, including 9,098 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.27 ( 5737 hom., cov: 33)

Exomes 𝑓: 0.30 ( 3361 hom. )

Consequence

LTBP2
NM_000428.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.220

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:

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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=-0.83).

BP6

Variant 14-74499066-G-A is Benign according to our data. Variant chr14-74499066-G-A is described in ClinVar as [Benign]. Clinvar id is 314246.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LTBP2	NM_000428.3 linkuse as main transcript	c.*1818C>T		3_prime_UTR_variant	36/36	ENST00000261978.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LTBP2	ENST00000261978.9 linkuse as main transcript	c.*1818C>T		3_prime_UTR_variant	36/36	1	NM_000428.3	P1

Frequencies

GnomAD3 genomes

AF:

0.266

AC:

40438

AN:

152006

Hom.:

5738

Cov.:

show subpopulations

Gnomad AFR

AF:

0.261

Gnomad AMI

AF:

0.152

Gnomad AMR

AF:

0.265

Gnomad ASJ

AF:

0.227

Gnomad EAS

AF:

0.570

Gnomad SAS

AF:

0.231

Gnomad FIN

AF:

0.222

Gnomad MID

AF:

0.411

Gnomad NFE

AF:

0.257

Gnomad OTH

AF:

0.301

GnomAD4 exome

AF:

0.301

AC:

19778

AN:

65816

Hom.:

3361

Cov.:

AF XY:

0.300

AC XY:

9139

AN XY:

30482

show subpopulations

Gnomad4 AFR exome

AF:

0.260

Gnomad4 AMR exome

AF:

0.255

Gnomad4 ASJ exome

AF:

0.240

Gnomad4 EAS exome

AF:

0.563

Gnomad4 SAS exome

AF:

0.204

Gnomad4 FIN exome

AF:

0.145

Gnomad4 NFE exome

AF:

0.254

Gnomad4 OTH exome

AF:

0.285

GnomAD4 genome

AF:

0.266

AC:

40450

AN:

152124

Hom.:

5737

Cov.:

AF XY:

0.264

AC XY:

19608

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.261

Gnomad4 AMR

AF:

0.265

Gnomad4 ASJ

AF:

0.227

Gnomad4 EAS

AF:

0.569

Gnomad4 SAS

AF:

0.233

Gnomad4 FIN

AF:

0.222

Gnomad4 NFE

AF:

0.257

Gnomad4 OTH

AF:

0.300

Alfa

AF:

0.261

Hom.:

1645

Bravo

AF:

0.274

Asia WGS

AF:

0.356

AC:

1238

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Weill-Marchesani syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Glaucoma 3, primary congenital, D

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

Cadd

Benign

1.6

Dann

Benign

0.54

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