5-136060980-T-C

Position:

• chr5-136060980-T-C

Variant summary

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

The NM_000358.3(TGFBI):​c.1906+44T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 1,402,796 control chromosomes in the GnomAD database, including 191,423 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Pathogenic (no stars).

• Frequency:
  • Genomes: 𝑓 0.56 (24747 hom., cov: 32)
  • Exomes 𝑓: 0.51 (166676 hom.)
• Consequence: TGFBI NM_000358.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.98

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 -8 ACMG points.

• PP5: Variant 5-136060980-T-C is Pathogenic according to our data. Variant chr5-136060980-T-C is described in Lovd as [Pathogenic].
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94). . Strength limited to SUPPORTING due to the PP5.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.712 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGFBI	NM_000358.3	c.1906+44T>C		intron_variant		ENST00000442011.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGFBI	ENST00000442011.7	c.1906+44T>C		intron_variant		1	NM_000358.3	P1

Frequencies

GnomAD3 genomes AF: 0.561 AC: 85159 AN: 151812 Hom.: 24710 Cov.: 32

Gnomad AFR AF: 0.718

Gnomad AMI AF: 0.375

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.595

Gnomad SAS AF: 0.520

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.562

GnomAD3 exomes AF: 0.535 AC: 105623 AN: 197328 Hom.: 28437 AF XY: 0.527 AC XY: 56711 AN XY: 107516

Gnomad AFR exome AF: 0.737

Gnomad AMR exome AF: 0.560

Gnomad ASJ exome AF: 0.482

Gnomad EAS exome AF: 0.602

Gnomad SAS exome AF: 0.516

Gnomad FIN exome AF: 0.511

Gnomad NFE exome AF: 0.503

Gnomad OTH exome AF: 0.527

GnomAD4 exome AF: 0.513 AC: 642246 AN: 1250866 Hom.: 166676 Cov.: 16 AF XY: 0.512 AC XY: 315836 AN XY: 616622

Gnomad4 AFR exome AF: 0.733

Gnomad4 AMR exome AF: 0.545

Gnomad4 ASJ exome AF: 0.472

Gnomad4 EAS exome AF: 0.616

Gnomad4 SAS exome AF: 0.519

Gnomad4 FIN exome AF: 0.511

Gnomad4 NFE exome AF: 0.502

Gnomad4 OTH exome AF: 0.525

GnomAD4 genome AF: 0.561 AC: 85260 AN: 151930 Hom.: 24747 Cov.: 32 AF XY: 0.558 AC XY: 41408 AN XY: 74262

Gnomad4 AFR AF: 0.718

Gnomad4 AMR AF: 0.502

Gnomad4 ASJ AF: 0.486

Gnomad4 EAS AF: 0.595

Gnomad4 SAS AF: 0.520

Gnomad4 FIN AF: 0.506

Gnomad4 NFE AF: 0.494

Gnomad4 OTH AF: 0.567

Alfa AF: 0.505 Hom.: 41872

Bravo AF: 0.574

Asia WGS AF: 0.588 AC: 2043 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.023
DANN	Benign	0.35

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: rs6880837; hg19: chr5-135396669;