Variant 5-136055685-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_000358.3(TGFBI):c.1416C>T(p.Leu472Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 1,600,388 control chromosomes in the GnomAD database, including 60,640 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6023 hom., cov: 33)

Exomes 𝑓: 0.27 ( 54617 hom. )

Consequence

TGFBI
NM_000358.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.26

Variant links:

Genes affected

TGFBI (HGNC:11771): (transforming growth factor beta induced) This gene encodes an RGD-containing protein that binds to type I, II and IV collagens. The RGD motif is found in many extracellular matrix proteins modulating cell adhesion and serves as a ligand recognition sequence for several integrins. This protein plays a role in cell-collagen interactions and may be involved in endochondrial bone formation in cartilage. The protein is induced by transforming growth factor-beta and acts to inhibit cell adhesion. Mutations in this gene are associated with multiple types of corneal dystrophy. [provided by RefSeq, Jul 2008]

TGFBI links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP7

Synonymous conserved (PhyloP=-1.26 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFBI	NM_000358.3 link	c.1416C>T	p.Leu472Leu	synonymous_variant	11/17	ENST00000442011.7	NP_000349.1	Q15582A0A0S2Z4Q2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFBI	ENST00000442011.7 link	c.1416C>T	p.Leu472Leu	synonymous_variant	11/17	1	NM_000358.3	ENSP00000416330.2		Q15582

Frequencies

GnomAD3 genomes

AF:

0.279

AC:

42491

AN:

152044

Hom.:

6021

Cov.:

show subpopulations

Gnomad AFR

AF:

0.311

Gnomad AMI

AF:

0.244

Gnomad AMR

AF:

0.229

Gnomad ASJ

AF:

0.301

Gnomad EAS

AF:

0.234

Gnomad SAS

AF:

0.362

Gnomad FIN

AF:

0.276

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.269

Gnomad OTH

AF:

0.285

GnomAD3 exomes

AF:

0.269

AC:

66294

AN:

246444

Hom.:

9203

AF XY:

0.275

AC XY:

36706

AN XY:

133592

show subpopulations

Gnomad AFR exome

AF:

0.312

Gnomad AMR exome

AF:

0.194

Gnomad ASJ exome

AF:

0.285

Gnomad EAS exome

AF:

0.221

Gnomad SAS exome

AF:

0.365

Gnomad FIN exome

AF:

0.270

Gnomad NFE exome

AF:

0.266

Gnomad OTH exome

AF:

0.272

GnomAD4 exome

AF:

0.273

AC:

394877

AN:

1448226

Hom.:

54617

Cov.:

AF XY:

0.275

AC XY:

197674

AN XY:

717814

show subpopulations

Gnomad4 AFR exome

AF:

0.321

Gnomad4 AMR exome

AF:

0.201

Gnomad4 ASJ exome

AF:

0.285

Gnomad4 EAS exome

AF:

0.248

Gnomad4 SAS exome

AF:

0.363

Gnomad4 FIN exome

AF:

0.271

Gnomad4 NFE exome

AF:

0.268

Gnomad4 OTH exome

AF:

0.278

GnomAD4 genome

AF:

0.279

AC:

42524

AN:

152162

Hom.:

6023

Cov.:

AF XY:

0.280

AC XY:

20793

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.311

Gnomad4 AMR

AF:

0.229

Gnomad4 ASJ

AF:

0.301

Gnomad4 EAS

AF:

0.234

Gnomad4 SAS

AF:

0.362

Gnomad4 FIN

AF:

0.276

Gnomad4 NFE

AF:

0.269

Gnomad4 OTH

AF:

0.285

Alfa

AF:

0.272

Hom.:

4113

Bravo

AF:

0.275

Asia WGS

AF:

0.293

AC:

1017

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Corneal dystrophy

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. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

6.8

DANN

Benign

0.80

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