Variant rs41298960 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000442011.7(TGFBI):c.460-16C>T variant causes a splice polypyrimidine tract, 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
ENST00000442011.7 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0800

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

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

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/exons	MANE	Protein	UniProt
TGFBI	NM_000358.3 linkuse as main transcript	c.460-16C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000442011.7	NP_000349.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris
TGFBI	ENST00000442011.7 linkuse as main transcript	c.460-16C>T	splice_polypyrimidine_tract_variant, intron_variant		1	NM_000358.3	ENSP00000416330	P1
TGFBI	ENST00000506699.5 linkuse as main transcript	n.864C>T	non_coding_transcript_exon_variant	4/17	2
TGFBI	ENST00000515433.1 linkuse as main transcript	n.1091C>T	non_coding_transcript_exon_variant	1/4	2
TGFBI	ENST00000507018.5 linkuse as main transcript	c.*53-16C>T	splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		5		ENSP00000421540

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

GnomAD3 exomes

AF:

0.0474

AC:

11600

AN:

244570

Hom.:

359

AF XY:

0.0495

AC XY:

6561

AN XY:

132594

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 SAS exome

AF:

0.0322

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

Gnomad4 AFR exome

AF:

0.0109

Gnomad4 AMR exome

AF:

0.0257

Gnomad4 ASJ exome

AF:

0.0467

Gnomad4 EAS exome

AF:

0.000177

Gnomad4 SAS exome

AF:

0.0348

Gnomad4 FIN exome

AF:

0.0552

Gnomad4 NFE exome

AF:

0.0746

Gnomad4 OTH exome

AF:

0.0545

GnomAD4 genome

AF:

0.0459

AC:

6979

AN:

152146

Hom.:

211

Cov.:

AF XY:

0.0440

AC XY:

3274

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.0124

Gnomad4 AMR

AF:

0.0363

Gnomad4 ASJ

AF:

0.0449

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.0284

Gnomad4 FIN

AF:

0.0517

Gnomad4 NFE

AF:

0.0722

Gnomad4 OTH

AF:

0.0469

Alfa

AF:

0.0562

Hom.:

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

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.9

DANN

Benign

0.46

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