5-136047300-G-C

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.651G>C(p.Leu217Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 1,613,546 control chromosomes in the GnomAD database, including 169,610 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 12501 hom., cov: 31)

Exomes 𝑓: 0.46 ( 157109 hom. )

Consequence

TGFBI
NM_000358.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.310

Publications

37 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=-0.55).

BP6

Variant 5-136047300-G-C is Benign according to our data. Variant chr5-136047300-G-C is described in ClinVar as [Benign]. Clinvar id is 255939.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.31 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFBI	NM_000358.3 link	c.651G>C	p.Leu217Leu	synonymous_variant	Exon 6 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.651G>C	p.Leu217Leu	synonymous_variant	Exon 6 of 17	1	NM_000358.3	ENSP00000416330.2		Q15582
TGFBI	ENST00000508767.5 link	c.-25G>C		upstream_gene_variant		3		ENSP00000423871.1		H0Y9D7

Frequencies

GnomAD3 genomes

AF:

0.367

AC:

55660

AN:

151786

Hom.:

12503

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0933

Gnomad AMI

AF:

0.603

Gnomad AMR

AF:

0.466

Gnomad ASJ

AF:

0.415

Gnomad EAS

AF:

0.374

Gnomad SAS

AF:

0.410

Gnomad FIN

AF:

0.491

Gnomad MID

AF:

0.382

Gnomad NFE

AF:

0.482

Gnomad OTH

AF:

0.362

GnomAD2 exomes

AF:

0.435

AC:

108413

AN:

249078

AF XY:

0.440

show subpopulations

Gnomad AFR exome

AF:

0.0852

Gnomad AMR exome

AF:

0.469

Gnomad ASJ exome

AF:

0.419

Gnomad EAS exome

AF:

0.379

Gnomad FIN exome

AF:

0.490

Gnomad NFE exome

AF:

0.476

Gnomad OTH exome

AF:

0.446

GnomAD4 exome

AF:

0.459

AC:

670261

AN:

1461642

Hom.:

157109

Cov.:

AF XY:

0.459

AC XY:

333432

AN XY:

727114

show subpopulations

African (AFR)

AF:

0.0785

AC:

2627

AN:

33480

American (AMR)

AF:

0.467

AC:

20875

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.426

AC:

11121

AN:

26132

East Asian (EAS)

AF:

0.365

AC:

14509

AN:

39700

South Asian (SAS)

AF:

0.424

AC:

36564

AN:

86252

European-Finnish (FIN)

AF:

0.487

AC:

26024

AN:

53384

Middle Eastern (MID)

AF:

0.406

AC:

2340

AN:

5766

European-Non Finnish (NFE)

AF:

0.477

AC:

530208

AN:

1111840

Other (OTH)

AF:

0.431

AC:

25993

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

21286

42571

63857

85142

106428

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.366

AC:

55655

AN:

151904

Hom.:

12501

Cov.:

AF XY:

0.371

AC XY:

27549

AN XY:

74208

show subpopulations

African (AFR)

AF:

0.0930

AC:

3857

AN:

41462

American (AMR)

AF:

0.466

AC:

7120

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.415

AC:

1437

AN:

3466

East Asian (EAS)

AF:

0.374

AC:

1918

AN:

5128

South Asian (SAS)

AF:

0.410

AC:

1972

AN:

4808

European-Finnish (FIN)

AF:

0.491

AC:

5165

AN:

10526

Middle Eastern (MID)

AF:

0.366

AC:

107

AN:

292

European-Non Finnish (NFE)

AF:

0.482

AC:

32777

AN:

67940

Other (OTH)

AF:

0.358

AC:

756

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1576

3152

4728

6304

7880

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.437

Hom.:

5034

Bravo

AF:

0.349

Asia WGS

AF:

0.346

AC:

1202

AN:

3478

EpiCase

AF:

0.484

EpiControl

AF:

0.474

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

Jan 28, 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

-0.55

CADD

Benign

8.3

(source)

DANN

Benign

0.71

PhyloP100

-0.31

PromoterAI

-0.0077

Neutral

(source)

Mutation Taster

=100/0

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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5-136047300-G-C

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