rs1054124

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. BP4BP6_Very_StrongBA1

The NM_000358.3(TGFBI):c.981A>G(p.Val327Val) variant causes a synonymous change. The variant allele was found at a frequency of 0.294 in 1,613,748 control chromosomes in the GnomAD database, including 72,709 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 10205 hom., cov: 33)

Exomes 𝑓: 0.29 ( 62504 hom. )

Consequence

TGFBI
NM_000358.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 5.79

Publications

33 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, STRONG Submitted by: Ambry Genetics, PanelApp Australia
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: G2P, Orphanet
Thiel-Behnke corneal dystrophy
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Orphanet
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.

BP4

Computational evidence support a benign effect (REVEL=0.244).

BP6

Variant 5-136052974-A-G is Benign according to our data. Variant chr5-136052974-A-G is described in ClinVar as Benign. ClinVar VariationId is 255940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.509 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFBI	NM_000358.3	MANE Select	c.981A>G	p.Val327Val	synonymous	Exon 8 of 17	NP_000349.1	Q15582

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TGFBI	ENST00000442011.7	TSL:1 MANE Select	c.981A>G	p.Val327Val	synonymous	Exon 8 of 17	ENSP00000416330.2	Q15582
TGFBI	ENST00000508767.5	TSL:3	c.239-44A>G		intron	N/A	ENSP00000423871.1	H0Y9D7
TGFBI	ENST00000514554.5	TSL:5	c.132A>G	p.Val44Val	synonymous	Exon 2 of 9	ENSP00000421440.1	H0Y8L3

Frequencies

GnomAD3 genomes

AF:

0.350

AC:

53240

AN:

152026

Hom.:

10188

Cov.:

show subpopulations

Gnomad AFR

AF:

0.515

Gnomad AMI

AF:

0.246

Gnomad AMR

AF:

0.319

Gnomad ASJ

AF:

0.302

Gnomad EAS

AF:

0.333

Gnomad SAS

AF:

0.372

Gnomad FIN

AF:

0.290

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.271

Gnomad OTH

AF:

0.350

GnomAD2 exomes

AF:

0.318

AC:

79241

AN:

249006

AF XY:

0.314

show subpopulations

Gnomad AFR exome

AF:

0.518

Gnomad AMR exome

AF:

0.375

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:

0.299

GnomAD4 exome

AF:

0.288

AC:

420650

AN:

1461604

Hom.:

62504

Cov.:

AF XY:

0.289

AC XY:

209986

AN XY:

727070

show subpopulations

African (AFR)

AF:

0.526

AC:

17619

AN:

33480

American (AMR)

AF:

0.370

AC:

16554

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.286

AC:

7464

AN:

26136

East Asian (EAS)

AF:

0.337

AC:

13377

AN:

39698

South Asian (SAS)

AF:

0.369

AC:

31848

AN:

86252

European-Finnish (FIN)

AF:

0.286

AC:

15279

AN:

53394

Middle Eastern (MID)

AF:

0.254

AC:

1466

AN:

5768

European-Non Finnish (NFE)

AF:

0.269

AC:

298664

AN:

1111800

Other (OTH)

AF:

0.304

AC:

18379

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

17593

35186

52780

70373

87966

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10258

20516

30774

41032

51290

<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:

0.350

AC:

53319

AN:

152144

Hom.:

10205

Cov.:

AF XY:

0.350

AC XY:

26030

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.515

AC:

21363

AN:

41504

American (AMR)

AF:

0.319

AC:

4884

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.302

AC:

1047

AN:

3468

East Asian (EAS)

AF:

0.333

AC:

1723

AN:

5172

South Asian (SAS)

AF:

0.372

AC:

1791

AN:

4814

European-Finnish (FIN)

AF:

0.290

AC:

3077

AN:

10596

Middle Eastern (MID)

AF:

0.252

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.271

AC:

18399

AN:

67978

Other (OTH)

AF:

0.349

AC:

737

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1744

3488

5233

6977

8721

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

522

1044

1566

2088

2610

<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:

0.310

Hom.:

5363

Bravo

AF:

0.360

Asia WGS

AF:

0.365

AC:

1267

AN:

3478

EpiCase

AF:

0.255

EpiControl

AF:

0.257

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Corneal dystrophy (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

8.5

(source)

DANN

Benign

0.67

PhyloP100

5.8

Mutation Taster

=65/35

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

Computational scores

Splicing

Publications

Other links and lift over