rs2073510

Positions:

• chr5-136047741-A-G
• chr5-136047741-A-T

Variant summary

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

The NM_000358.3(TGFBI):​c.771+321A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 298,946 control chromosomes in the GnomAD database, including 15,995 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 0.34 (9117 hom., cov: 33)
  • Exomes 𝑓: 0.30 (6878 hom.)
• Consequence: TGFBI NM_000358.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFBI	NM_000358.3	c.771+321A>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.771+321A>G		intron_variant		1	NM_000358.3	ENSP00000416330.2
TGFBI	ENST00000508767.5	c.96+321A>G		intron_variant		3		ENSP00000423871.1

Frequencies

GnomAD3 genomes AF: 0.336 AC: 51081 AN: 151976 Hom.: 9103 Cov.: 33

Gnomad AFR AF: 0.460

Gnomad AMI AF: 0.244

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.336

GnomAD4 exome AF: 0.299 AC: 43853 AN: 146852 Hom.: 6878 Cov.: 0 AF XY: 0.301 AC XY: 22487 AN XY: 74796

Gnomad4 AFR exome AF: 0.455

Gnomad4 AMR exome AF: 0.345

Gnomad4 ASJ exome AF: 0.295

Gnomad4 EAS exome AF: 0.337

Gnomad4 SAS exome AF: 0.368

Gnomad4 FIN exome AF: 0.309

Gnomad4 NFE exome AF: 0.271

Gnomad4 OTH exome AF: 0.303

GnomAD4 genome AF: 0.336 AC: 51147 AN: 152094 Hom.: 9117 Cov.: 33 AF XY: 0.337 AC XY: 25041 AN XY: 74362

Gnomad4 AFR AF: 0.460

Gnomad4 AMR AF: 0.312

Gnomad4 ASJ AF: 0.301

Gnomad4 EAS AF: 0.333

Gnomad4 SAS AF: 0.373

Gnomad4 FIN AF: 0.309

Gnomad4 NFE AF: 0.271

Gnomad4 OTH AF: 0.335

Alfa AF: 0.323 Hom.: 1016

Bravo AF: 0.343

Asia WGS AF: 0.360 AC: 1250 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.023
DANN	Benign	0.62

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: rs2073510; hg19: chr5-135383430;