5-136058065-T-C

Variant names:

• chr5-136058065-T-C
• rs3792900
• NM_000358.3:c.1679-1025T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000358.3(TGFBI):​c.1679-1025T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 151,752 control chromosomes in the GnomAD database, including 27,224 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.58 (27224 hom., cov: 30)
• Consequence: TGFBI NM_000358.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.370
• Publications: 11 publications found

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 Submitted by: Ambry Genetics
• 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: Orphanet, G2P
• Thiel-Behnke corneal dystrophy

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
• epithelial basement membrane dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.827 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFBI	NM_000358.3	MANE Select	c.1679-1025T>C		intron	N/A	NP_000349.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFBI	ENST00000442011.7	TSL:1 MANE Select	c.1679-1025T>C		intron	N/A	ENSP00000416330.2
	TGFBI	ENST00000514554.5	TSL:5	c.830-1025T>C		intron	N/A	ENSP00000421440.1
	TGFBI	ENST00000506699.5	TSL:2	n.2196-1025T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.575 AC: 87139 AN: 151634 Hom.: 27164 Cov.: 30

Gnomad AFR AF: 0.834

Gnomad AMI AF: 0.375

Gnomad AMR AF: 0.477

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.577

Gnomad SAS AF: 0.504

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.467

Gnomad OTH AF: 0.567

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.575 AC: 87267 AN: 151752 Hom.: 27224 Cov.: 30 AF XY: 0.570 AC XY: 42271 AN XY: 74098

African (AFR) AF: 0.835 AC: 34568 AN: 41422

American (AMR) AF: 0.477 AC: 7283 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.477 AC: 1654 AN: 3468

East Asian (EAS) AF: 0.577 AC: 2955 AN: 5118

South Asian (SAS) AF: 0.503 AC: 2409 AN: 4786

European-Finnish (FIN) AF: 0.481 AC: 5057 AN: 10514

Middle Eastern (MID) AF: 0.455 AC: 133 AN: 292

European-Non Finnish (NFE) AF: 0.467 AC: 31662 AN: 67862

Other (OTH) AF: 0.572 AC: 1205 AN: 2108

Alfa AF: 0.536 Hom.: 3973

Bravo AF: 0.589

Asia WGS AF: 0.586 AC: 2038 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.7
DANN	Benign	0.77
PhyloP100		0.37
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3792900; hg19: chr5-135393754;