Variant 5-136047300-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_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

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=-0.55).

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/exons	MANE	Protein	UniProt
TGFBI	NM_000358.3 link	c.651G>C	p.Leu217Leu	synonymous_variant	6/17	ENST00000442011.7	NP_000349.1	Q15582A0A0S2Z4Q2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFBI	ENST00000442011.7 link	c.651G>C	p.Leu217Leu	synonymous_variant	6/17	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

GnomAD3 exomes

AF:

0.435

AC:

108413

AN:

249078

Hom.:

24831

AF XY:

0.440

AC XY:

59504

AN XY:

135142

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 SAS exome

AF:

0.423

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

Gnomad4 AFR exome

AF:

0.0785

Gnomad4 AMR exome

AF:

0.467

Gnomad4 ASJ exome

AF:

0.426

Gnomad4 EAS exome

AF:

0.365

Gnomad4 SAS exome

AF:

0.424

Gnomad4 FIN exome

AF:

0.487

Gnomad4 NFE exome

AF:

0.477

Gnomad4 OTH exome

AF:

0.431

GnomAD4 genome

AF:

0.366

AC:

55655

AN:

151904

Hom.:

12501

Cov.:

AF XY:

0.371

AC XY:

27549

AN XY:

74208

show subpopulations

Gnomad4 AFR

AF:

0.0930

Gnomad4 AMR

AF:

0.466

Gnomad4 ASJ

AF:

0.415

Gnomad4 EAS

AF:

0.374

Gnomad4 SAS

AF:

0.410

Gnomad4 FIN

AF:

0.491

Gnomad4 NFE

AF:

0.482

Gnomad4 OTH

AF:

0.358

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

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

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

8.3

DANN

Benign

0.71

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