rs756463

Positions:

• chr5-136032068-C-T

Variant summary

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

The NM_000358.3(TGFBI):​c.135-1695C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 152,058 control chromosomes in the GnomAD database, including 7,521 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 0.31 (7521 hom., cov: 32)
• Consequence: TGFBI NM_000358.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0570

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFBI	NM_000358.3	c.135-1695C>T		intron_variant		ENST00000442011.7	NP_000349.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFBI	ENST00000442011.7	c.135-1695C>T		intron_variant		1	NM_000358.3	ENSP00000416330	P1
TGFBI	ENST00000507018.5	c.52-1695C>T		intron_variant, NMD_transcript_variant		5		ENSP00000421540
TGFBI	ENST00000504185.5	n.203-1695C>T		intron_variant, non_coding_transcript_variant		4
TGFBI	ENST00000506699.5	n.200-1695C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46684 AN: 151940 Hom.: 7514 Cov.: 32

Gnomad AFR AF: 0.400

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.277

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.300

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

GnomAD4 genome AF: 0.307 AC: 46726 AN: 152058 Hom.: 7521 Cov.: 32 AF XY: 0.306 AC XY: 22762 AN XY: 74326

Gnomad4 AFR AF: 0.400

Gnomad4 AMR AF: 0.368

Gnomad4 ASJ AF: 0.277

Gnomad4 EAS AF: 0.372

Gnomad4 SAS AF: 0.189

Gnomad4 FIN AF: 0.232

Gnomad4 NFE AF: 0.256

Gnomad4 OTH AF: 0.304

Alfa AF: 0.275 Hom.: 5567

Bravo AF: 0.323

Asia WGS AF: 0.315 AC: 1096 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.2
DANN	Benign	0.33

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: rs756463; hg19: chr5-135367757;