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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000358.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFBI	NM_000358.3	MANE Select	c.651G>C	p.Leu217Leu	synonymous	Exon 6 of 17	NP_000349.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TGFBI	ENST00000442011.7	TSL:1 MANE Select	c.651G>C	p.Leu217Leu	synonymous	Exon 6 of 17	ENSP00000416330.2
TGFBI	ENST00000506699.5	TSL:2	n.1071G>C		non_coding_transcript_exon	Exon 5 of 17
TGFBI	ENST00000507018.5	TSL:5	n.*244G>C		non_coding_transcript_exon	Exon 6 of 17	ENSP00000421540.1

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

Age Distribution

Exome Het

Exome Hom

Variant carriers

15480

30960

46440

61920

77400

<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:

0.366

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

Age Distribution

Genome Het

Genome Hom

Variant carriers

532

1064

1596

2128

2660

<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:

0.437

Hom.:

5034

Bravo

AF:

0.349

Asia WGS

AF:

0.346

AC:

1202

AN:

3478

EpiCase

AF:

0.484

EpiControl

AF:

0.474

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Corneal dystrophy (1)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over