rs1133170

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_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

Publications

34 publications found

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 Gene-Disease associations (from GenCC):

epithelial-stromal TGFBI dystrophy
Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics
granular corneal dystrophy type I
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P
granular corneal dystrophy type II
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
lattice corneal dystrophy type I
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Orphanet
Reis-Bucklers corneal dystrophy
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
Thiel-Behnke corneal dystrophy
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
epithelial basement membrane dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

TGFBI links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

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

BP6

Variant 5-136055685-C-T is Benign according to our data. Variant chr5-136055685-C-T is described in ClinVar as Benign. ClinVar VariationId is 255936.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
TGFBI	NM_000358.3 link	c.1416C>T	p.Leu472Leu	synonymous_variant	Exon 11 of 17	ENST00000442011.7	NP_000349.1	Q15582A0A0S2Z4Q2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFBI	ENST00000442011.7 link	c.1416C>T	p.Leu472Leu	synonymous_variant	Exon 11 of 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

GnomAD2 exomes

AF:

0.269

AC:

66294

AN:

246444

AF XY:

0.275

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 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

African (AFR)

AF:

0.321

AC:

10702

AN:

33300

American (AMR)

AF:

0.201

AC:

8898

AN:

44376

Ashkenazi Jewish (ASJ)

AF:

0.285

AC:

7398

AN:

25944

East Asian (EAS)

AF:

0.248

AC:

9763

AN:

39318

South Asian (SAS)

AF:

0.363

AC:

30920

AN:

85176

European-Finnish (FIN)

AF:

0.271

AC:

14420

AN:

53150

Middle Eastern (MID)

AF:

0.238

AC:

1363

AN:

5736

European-Non Finnish (NFE)

AF:

0.268

AC:

294813

AN:

1101590

Other (OTH)

AF:

0.278

AC:

16600

AN:

59636

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

13506

27012

40517

54023

67529

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10046

20092

30138

40184

50230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.279

AC:

42524

AN:

152162

Hom.:

6023

Cov.:

AF XY:

0.280

AC XY:

20793

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.311

AC:

12892

AN:

41496

American (AMR)

AF:

0.229

AC:

3507

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.301

AC:

1046

AN:

3470

East Asian (EAS)

AF:

0.234

AC:

1209

AN:

5176

South Asian (SAS)

AF:

0.362

AC:

1746

AN:

4818

European-Finnish (FIN)

AF:

0.276

AC:

2921

AN:

10578

Middle Eastern (MID)

AF:

0.238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.269

AC:

18309

AN:

68018

Other (OTH)

AF:

0.285

AC:

602

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1651

3301

4952

6602

8253

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

452

904

1356

1808

2260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.272

Hom.:

4538

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

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Corneal dystrophy

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

6.8

(source)

DANN

Benign

0.80

PhyloP100

-1.3

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over