rs756462

chr5-136032256-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000358.3(TGFBI):c.135-1507T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 152,000 control chromosomes in the GnomAD database, including 5,903 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 0.26 (5903 hom., cov: 32)
• Consequence: TGFBI NM_000358.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.230

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGFBI	NM_000358.3	c.135-1507T>C		intron_variant		ENST00000442011.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGFBI	ENST00000442011.7	c.135-1507T>C		intron_variant		1	NM_000358.3	P1
TGFBI	ENST00000507018.5	c.52-1507T>C		intron_variant, NMD_transcript_variant		5
TGFBI	ENST00000504185.5	n.203-1507T>C		intron_variant, non_coding_transcript_variant		4
TGFBI	ENST00000506699.5	n.200-1507T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39882 AN: 151882 Hom.: 5892 Cov.: 32

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.251

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

GnomAD4 genome AF: 0.263 AC: 39927 AN: 152000 Hom.: 5903 Cov.: 32 AF XY: 0.262 AC XY: 19505 AN XY: 74310

Gnomad4 AFR AF: 0.391

Gnomad4 AMR AF: 0.318

Gnomad4 ASJ AF: 0.179

Gnomad4 EAS AF: 0.370

Gnomad4 SAS AF: 0.139

Gnomad4 FIN AF: 0.184

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.256

Alfa AF: 0.177 Hom.: 1213

Bravo AF: 0.280

Asia WGS AF: 0.298 AC: 1040 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	3.4
Dann	Benign	0.73

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

Other links and lift over

dbSNP: rs756462; hg19: chr5-135367945;