5-136061329-T-C

Variant names:

• chr5-136061329-T-C
• rs2302038
• NM_000358.3:c.1907-171T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000358.3(TGFBI):​c.1907-171T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 626,616 control chromosomes in the GnomAD database, including 92,961 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 0.59 (28180 hom., cov: 32)
  • Exomes 𝑓: 0.52 (64781 hom.)
• Consequence: TGFBI NM_000358.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.23
• Publications: 13 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFBI	NM_000358.3	c.1907-171T>C		intron_variant	Intron 14 of 16	ENST00000442011.7	NP_000349.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFBI	ENST00000442011.7	c.1907-171T>C		intron_variant	Intron 14 of 16	1	NM_000358.3	ENSP00000416330.2

Frequencies

GnomAD3 genomes AF: 0.590 AC: 89692 AN: 151892 Hom.: 28135 Cov.: 32

Gnomad AFR AF: 0.821

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.596

Gnomad SAS AF: 0.525

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.582

GnomAD4 exome AF: 0.517 AC: 245407 AN: 474606 Hom.: 64781 Cov.: 5 AF XY: 0.513 AC XY: 129232 AN XY: 251728

African (AFR) AF: 0.818 AC: 10956 AN: 13386

American (AMR) AF: 0.537 AC: 14104 AN: 26268

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 6966 AN: 14930

East Asian (EAS) AF: 0.615 AC: 18767 AN: 30510

South Asian (SAS) AF: 0.512 AC: 25198 AN: 49212

European-Finnish (FIN) AF: 0.506 AC: 15482 AN: 30582

Middle Eastern (MID) AF: 0.476 AC: 1130 AN: 2374

European-Non Finnish (NFE) AF: 0.494 AC: 138643 AN: 280618

Other (OTH) AF: 0.530 AC: 14161 AN: 26726

GnomAD4 genome AF: 0.591 AC: 89802 AN: 152010 Hom.: 28180 Cov.: 32 AF XY: 0.586 AC XY: 43548 AN XY: 74292

African (AFR) AF: 0.821 AC: 34021 AN: 41458

American (AMR) AF: 0.512 AC: 7827 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.487 AC: 1689 AN: 3468

East Asian (EAS) AF: 0.596 AC: 3070 AN: 5150

South Asian (SAS) AF: 0.525 AC: 2523 AN: 4804

European-Finnish (FIN) AF: 0.506 AC: 5344 AN: 10566

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.494 AC: 33613 AN: 67974

Other (OTH) AF: 0.586 AC: 1238 AN: 2112

Alfa AF: 0.519 Hom.: 13990

Bravo AF: 0.607

Asia WGS AF: 0.598 AC: 2082 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.012
DANN	Benign	0.72
PhyloP100		-3.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs2302038; hg19: chr5-135397018; COSMIC: COSV59352403; COSMIC: COSV59352403;