rs41298960

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000358.3(TGFBI):c.460-16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0632 in 1,608,954 control chromosomes in the GnomAD database, including 3,634 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.046 ( 211 hom., cov: 32)

Exomes 𝑓: 0.065 ( 3423 hom. )

Consequence

TGFBI
NM_000358.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0800

Publications

4 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 5-136046835-C-T is Benign according to our data. Variant chr5-136046835-C-T is described in ClinVar as Benign. ClinVar VariationId is 255938.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFBI	NM_000358.3 link	c.460-16C>T		intron_variant	Intron 4 of 16	ENST00000442011.7	NP_000349.1	Q15582A0A0S2Z4Q2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TGFBI	ENST00000442011.7 link	c.460-16C>T	intron_variant	Intron 4 of 16	1	NM_000358.3	ENSP00000416330.2	Q15582
TGFBI	ENST00000506699.5 link	n.864C>T	non_coding_transcript_exon_variant	Exon 4 of 17	2
TGFBI	ENST00000515433.1 link	n.1091C>T	non_coding_transcript_exon_variant	Exon 1 of 4	2
TGFBI	ENST00000507018.5 link	n.*53-16C>T	intron_variant	Intron 4 of 16	5		ENSP00000421540.1	H0Y8M8

Frequencies

GnomAD3 genomes

AF:

0.0459

AC:

6981

AN:

152028

Hom.:

211

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0124

Gnomad AMI

AF:

0.0592

Gnomad AMR

AF:

0.0363

Gnomad ASJ

AF:

0.0449

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.0282

Gnomad FIN

AF:

0.0517

Gnomad MID

AF:

0.0191

Gnomad NFE

AF:

0.0722

Gnomad OTH

AF:

0.0479

GnomAD2 exomes

AF:

0.0474

AC:

11600

AN:

244570

AF XY:

0.0495

show subpopulations

Gnomad AFR exome

AF:

0.0118

Gnomad AMR exome

AF:

0.0235

Gnomad ASJ exome

AF:

0.0499

Gnomad EAS exome

AF:

0.000111

Gnomad FIN exome

AF:

0.0535

Gnomad NFE exome

AF:

0.0700

Gnomad OTH exome

AF:

0.0518

GnomAD4 exome

AF:

0.0651

AC:

94777

AN:

1456808

Hom.:

3423

Cov.:

AF XY:

0.0643

AC XY:

46547

AN XY:

724166

show subpopulations

African (AFR)

AF:

0.0109

AC:

364

AN:

33432

American (AMR)

AF:

0.0257

AC:

1145

AN:

44502

Ashkenazi Jewish (ASJ)

AF:

0.0467

AC:

1204

AN:

25754

East Asian (EAS)

AF:

0.000177

AC:

AN:

39612

South Asian (SAS)

AF:

0.0348

AC:

2981

AN:

85588

European-Finnish (FIN)

AF:

0.0552

AC:

2932

AN:

53154

Middle Eastern (MID)

AF:

0.0252

AC:

144

AN:

5714

European-Non Finnish (NFE)

AF:

0.0746

AC:

82720

AN:

1108842

Other (OTH)

AF:

0.0545

AC:

3280

AN:

60210

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

4232

8465

12697

16930

21162

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3008

6016

9024

12032

15040

<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:

0.0459

AC:

6979

AN:

152146

Hom.:

211

Cov.:

AF XY:

0.0440

AC XY:

3274

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.0124

AC:

515

AN:

41530

American (AMR)

AF:

0.0363

AC:

555

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0449

AC:

156

AN:

3472

East Asian (EAS)

AF:

0.000194

AC:

AN:

5142

South Asian (SAS)

AF:

0.0284

AC:

137

AN:

4818

European-Finnish (FIN)

AF:

0.0517

AC:

548

AN:

10602

Middle Eastern (MID)

AF:

0.0240

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0722

AC:

4907

AN:

67970

Other (OTH)

AF:

0.0469

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

341

683

1024

1366

1707

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

160

240

320

400

<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:

0.0483

Hom.:

133

Bravo

AF:

0.0439

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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

- -

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

-0.82

CADD

Benign

2.9

(source)

DANN

Benign

0.46

PhyloP100

0.080

PromoterAI

-0.0092

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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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