5-136052974-A-C

Variant names:

• chr5-136052974-A-C
• rs1054124
• NM_000358.3:c.981A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000358.3(TGFBI):​c.981A>C​(p.Val327Val) variant causes a synonymous change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. V327V) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TGFBI NM_000358.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.79
• Publications: 33 publications found

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 Gene-Disease associations (from GenCC):

• epithelial-stromal TGFBI dystrophy

  Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics
• granular corneal dystrophy type I

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P
• granular corneal dystrophy type II

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
• lattice corneal dystrophy type I

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Orphanet
• Reis-Bucklers corneal dystrophy

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
• Thiel-Behnke corneal dystrophy

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
• epithelial basement membrane dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFBI	NM_000358.3	c.981A>C	p.Val327Val	synonymous_variant	Exon 8 of 17	ENST00000442011.7	NP_000349.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFBI	ENST00000442011.7	c.981A>C	p.Val327Val	synonymous_variant	Exon 8 of 17	1	NM_000358.3	ENSP00000416330.2
TGFBI	ENST00000508767.5	c.239-44A>C		intron_variant	Intron 2 of 4	3		ENSP00000423871.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 5363

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	7.9
DANN	Benign	0.66
PhyloP100		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs1054124; hg19: chr5-135388663;