rs4669

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP6_Very_StrongBP7BA1

The NM_000358.3(TGFBI):c.1620T>C(p.Phe540Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 1,613,520 control chromosomes in the GnomAD database, including 77,797 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 12807 hom., cov: 31)

Exomes 𝑓: 0.29 ( 64990 hom. )

Consequence

TGFBI
NM_000358.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.359

Publications

59 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 -17 ACMG points.

BP6

Variant 5-136056737-T-C is Benign according to our data. Variant chr5-136056737-T-C is described in ClinVar as Benign. ClinVar VariationId is 255937.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.359 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFBI	NM_000358.3 link	c.1620T>C	p.Phe540Phe	synonymous_variant	Exon 12 of 17	ENST00000442011.7	NP_000349.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFBI	ENST00000442011.7 link	c.1620T>C	p.Phe540Phe	synonymous_variant	Exon 12 of 17	1	NM_000358.3	ENSP00000416330.2

Frequencies

GnomAD3 genomes

AF:

0.380

AC:

57714

AN:

151768

Hom.:

12766

Cov.:

show subpopulations

Gnomad AFR

AF:

0.622

Gnomad AMI

AF:

0.244

Gnomad AMR

AF:

0.328

Gnomad ASJ

AF:

0.302

Gnomad EAS

AF:

0.332

Gnomad SAS

AF:

0.372

Gnomad FIN

AF:

0.290

Gnomad MID

AF:

0.236

Gnomad NFE

AF:

0.271

Gnomad OTH

AF:

0.366

GnomAD2 exomes

AF:

0.326

AC:

81231

AN:

248942

AF XY:

0.320

show subpopulations

Gnomad AFR exome

AF:

0.633

Gnomad AMR exome

AF:

0.380

Gnomad ASJ exome

AF:

0.285

Gnomad EAS exome

AF:

0.322

Gnomad FIN exome

AF:

0.286

Gnomad NFE exome

AF:

0.269

Gnomad OTH exome

AF:

0.304

GnomAD4 exome

AF:

0.291

AC:

425210

AN:

1461634

Hom.:

64990

Cov.:

AF XY:

0.291

AC XY:

211950

AN XY:

727108

show subpopulations

African (AFR)

AF:

0.639

AC:

21407

AN:

33480

American (AMR)

AF:

0.375

AC:

16790

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.286

AC:

7463

AN:

26132

East Asian (EAS)

AF:

0.337

AC:

13378

AN:

39698

South Asian (SAS)

AF:

0.370

AC:

31878

AN:

86244

European-Finnish (FIN)

AF:

0.286

AC:

15280

AN:

53392

Middle Eastern (MID)

AF:

0.260

AC:

1498

AN:

5768

European-Non Finnish (NFE)

AF:

0.269

AC:

298678

AN:

1111836

Other (OTH)

AF:

0.312

AC:

18838

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

16509

33018

49528

66037

82546

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10288

20576

30864

41152

51440

<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:

0.381

AC:

57823

AN:

151886

Hom.:

12807

Cov.:

AF XY:

0.379

AC XY:

28122

AN XY:

74232

show subpopulations

African (AFR)

AF:

0.622

AC:

25756

AN:

41396

American (AMR)

AF:

0.328

AC:

5009

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.302

AC:

1047

AN:

3470

East Asian (EAS)

AF:

0.332

AC:

1711

AN:

5152

South Asian (SAS)

AF:

0.372

AC:

1783

AN:

4794

European-Finnish (FIN)

AF:

0.290

AC:

3057

AN:

10548

Middle Eastern (MID)

AF:

0.260

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.271

AC:

18394

AN:

67944

Other (OTH)

AF:

0.365

AC:

768

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1633

3267

4900

6534

8167

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

540

1080

1620

2160

2700

<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:

0.298

Hom.:

21535

Bravo

AF:

0.396

Asia WGS

AF:

0.373

AC:

1296

AN:

3478

EpiCase

AF:

0.256

EpiControl

AF:

0.257

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 13, 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

-0.65

CADD

Benign

2.7

(source)

DANN

Benign

0.46

PhyloP100

-0.36

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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