5-136057508-A-G

Position:

• chr5-136057508-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP5 BP4 BA1

The NM_000358.3(TGFBI):​c.1678+713A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 151,756 control chromosomes in the GnomAD database, including 12,802 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Pathogenic (no stars).

• Frequency: Genomes: 𝑓 0.38 (12802 hom., cov: 30)
• Consequence: TGFBI NM_000358.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.334

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• PP5: Variant 5-136057508-A-G is Pathogenic according to our data. Variant chr5-136057508-A-G is described in Lovd as [Pathogenic].
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9). . Strength limited to SUPPORTING due to the PP5.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.617 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFBI	NM_000358.3	c.1678+713A>G		intron_variant		ENST00000442011.7	NP_000349.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFBI	ENST00000442011.7	c.1678+713A>G		intron_variant		1	NM_000358.3	ENSP00000416330.2

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57697 AN: 151638 Hom.: 12762 Cov.: 30

Gnomad AFR AF: 0.622

Gnomad AMI AF: 0.244

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.366

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

GnomAD4 genome AF: 0.381 AC: 57805 AN: 151756 Hom.: 12802 Cov.: 30 AF XY: 0.379 AC XY: 28110 AN XY: 74154

Gnomad4 AFR AF: 0.623

Gnomad4 AMR AF: 0.328

Gnomad4 ASJ AF: 0.302

Gnomad4 EAS AF: 0.330

Gnomad4 SAS AF: 0.372

Gnomad4 FIN AF: 0.291

Gnomad4 NFE AF: 0.271

Gnomad4 OTH AF: 0.365

Alfa AF: 0.257 Hom.: 942

Bravo AF: 0.396

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.34

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: rs6871571; hg19: chr5-135393197;