Variant 5-136052974-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000358.3(TGFBI):c.981A>G(p.Val327=) 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

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 5-136052974-A-G is Benign according to our data. Variant chr5-136052974-A-G is described in ClinVar as [Benign]. Clinvar id is 255940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-136052974-A-G is described in Lovd as [Benign]. Variant chr5-136052974-A-G is described in Lovd as [Pathogenic].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFBI	NM_000358.3 linkuse as main transcript	c.981A>G	p.Val327=	synonymous_variant	8/17	ENST00000442011.7	NP_000349.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFBI	ENST00000442011.7 linkuse as main transcript	c.981A>G	p.Val327=	synonymous_variant	8/17	1	NM_000358.3	ENSP00000416330	P1

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

GnomAD3 exomes

AF:

0.318

AC:

79241

AN:

249006

Hom.:

13229

AF XY:

0.314

AC XY:

42369

AN XY:

135064

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 SAS exome

AF:

0.370

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

Gnomad4 AFR exome

AF:

0.526

Gnomad4 AMR exome

AF:

0.370

Gnomad4 ASJ exome

AF:

0.286

Gnomad4 EAS exome

AF:

0.337

Gnomad4 SAS exome

AF:

0.369

Gnomad4 FIN exome

AF:

0.286

Gnomad4 NFE exome

AF:

0.269

Gnomad4 OTH exome

AF:

0.304

GnomAD4 genome

AF:

0.350

AC:

53319

AN:

152144

Hom.:

10205

Cov.:

AF XY:

0.350

AC XY:

26030

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.515

Gnomad4 AMR

AF:

0.319

Gnomad4 ASJ

AF:

0.302

Gnomad4 EAS

AF:

0.333

Gnomad4 SAS

AF:

0.372

Gnomad4 FIN

AF:

0.290

Gnomad4 NFE

AF:

0.271

Gnomad4 OTH

AF:

0.349

Alfa

AF:

0.310

Hom.:

4327

Bravo

AF:

0.360

Asia WGS

AF:

0.365

AC:

1267

AN:

3478

EpiCase

AF:

0.255

EpiControl

AF:

0.257

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 21, 2021	- -

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 12, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

8.5

DANN

Benign

0.67

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