Variant 14-74498927-T-C 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.*1957A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0251 in 225,244 control chromosomes in the GnomAD database, including 152 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.030 ( 127 hom., cov: 33)

Exomes 𝑓: 0.015 ( 25 hom. )

Consequence

LTBP2
NM_000428.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.125

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=-0.49).

BP6

Variant 14-74498927-T-C is Benign according to our data. Variant chr14-74498927-T-C is described in ClinVar as [Benign]. Clinvar id is 314245.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0696 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.*1957A>G		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.*1957A>G		3_prime_UTR_variant	36/36	1	NM_000428.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0298

AC:

4541

AN:

152230

Hom.:

124

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0716

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0132

Gnomad ASJ

AF:

0.0199

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.00600

Gnomad FIN

AF:

0.0201

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0147

Gnomad OTH

AF:

0.0253

GnomAD4 exome

AF:

0.0151

AC:

1100

AN:

72896

Hom.:

Cov.:

AF XY:

0.0148

AC XY:

498

AN XY:

33608

show subpopulations

Gnomad4 AFR exome

AF:

0.0739

Gnomad4 AMR exome

AF:

0.0148

Gnomad4 ASJ exome

AF:

0.0165

Gnomad4 EAS exome

AF:

0.00155

Gnomad4 SAS exome

AF:

0.00313

Gnomad4 FIN exome

AF:

0.0208

Gnomad4 NFE exome

AF:

0.0134

Gnomad4 OTH exome

AF:

0.0170

GnomAD4 genome

AF:

0.0299

AC:

4555

AN:

152348

Hom.:

127

Cov.:

AF XY:

0.0292

AC XY:

2174

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.0717

Gnomad4 AMR

AF:

0.0131

Gnomad4 ASJ

AF:

0.0199

Gnomad4 EAS

AF:

0.00173

Gnomad4 SAS

AF:

0.00600

Gnomad4 FIN

AF:

0.0201

Gnomad4 NFE

AF:

0.0147

Gnomad4 OTH

AF:

0.0250

Alfa

AF:

0.0209

Hom.:

Bravo

AF:

0.0322

Asia WGS

AF:

0.0110

AC:

AN:

3478

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 12, 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 12, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

Cadd

Benign

9.8

Dann

Benign

0.87

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