rs4669

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_000358.3(TGFBI):c.1620T>C(p.Phe540=) 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. In-silico tool predicts a benign outcome for this variant. 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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

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/exons	MANE	UniProt
TGFBI	NM_000358.3 linkuse as main transcript	c.1620T>C	p.Phe540=	synonymous_variant	12/17	ENST00000442011.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGFBI	ENST00000442011.7 linkuse as main transcript	c.1620T>C	p.Phe540=	synonymous_variant	12/17	1	NM_000358.3	P1

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

GnomAD3 exomes

AF:

0.326

AC:

81231

AN:

248942

Hom.:

14356

AF XY:

0.320

AC XY:

43184

AN XY:

135060

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 SAS exome

AF:

0.371

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

Gnomad4 AFR exome

AF:

0.639

Gnomad4 AMR exome

AF:

0.375

Gnomad4 ASJ exome

AF:

0.286

Gnomad4 EAS exome

AF:

0.337

Gnomad4 SAS exome

AF:

0.370

Gnomad4 FIN exome

AF:

0.286

Gnomad4 NFE exome

AF:

0.269

Gnomad4 OTH exome

AF:

0.312

GnomAD4 genome

AF:

0.381

AC:

57823

AN:

151886

Hom.:

12807

Cov.:

AF XY:

0.379

AC XY:

28122

AN XY:

74232

show subpopulations

Gnomad4 AFR

AF:

0.622

Gnomad4 AMR

AF:

0.328

Gnomad4 ASJ

AF:

0.302

Gnomad4 EAS

AF:

0.332

Gnomad4 SAS

AF:

0.372

Gnomad4 FIN

AF:

0.290

Gnomad4 NFE

AF:

0.271

Gnomad4 OTH

AF:

0.365

Alfa

AF:

0.289

Hom.:

13797

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

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Corneal dystrophy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

Cadd

Benign

2.7

Dann

Benign

0.46

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over