5-136060980-T-C

Variant names:

• chr5-136060980-T-C
• rs6880837
• NM_000358.3:c.1906+44T>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.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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 21 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, STRONG Submitted by: Ambry Genetics, PanelApp Australia
• 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: G2P, Orphanet
• Thiel-Behnke corneal dystrophy

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Orphanet
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.712 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000358.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFBI	NM_000358.3	MANE Select	c.1906+44T>C		intron	N/A	NP_000349.1	Q15582

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFBI	ENST00000442011.7	TSL:1 MANE Select	c.1906+44T>C		intron	N/A	ENSP00000416330.2	Q15582
	TGFBI	ENST00000514554.5	TSL:5	c.1057+44T>C		intron	N/A	ENSP00000421440.1	H0Y8L3
	TGFBI	ENST00000503087.1	TSL:3	c.130+44T>C		intron	N/A	ENSP00000427137.1	H0YAH8

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

GnomAD2 exomes AF: 0.535 AC: 105623 AN: 197328 AF XY: 0.527

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 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

African (AFR) AF: 0.733 AC: 20733 AN: 28282

American (AMR) AF: 0.545 AC: 16067 AN: 29460

Ashkenazi Jewish (ASJ) AF: 0.472 AC: 10201 AN: 21598

East Asian (EAS) AF: 0.616 AC: 23097 AN: 37524

South Asian (SAS) AF: 0.519 AC: 32378 AN: 62328

European-Finnish (FIN) AF: 0.511 AC: 25389 AN: 49662

Middle Eastern (MID) AF: 0.463 AC: 2366 AN: 5108

European-Non Finnish (NFE) AF: 0.502 AC: 484743 AN: 964948

Other (OTH) AF: 0.525 AC: 27272 AN: 51956

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

African (AFR) AF: 0.718 AC: 29753 AN: 41416

American (AMR) AF: 0.502 AC: 7670 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.486 AC: 1684 AN: 3462

East Asian (EAS) AF: 0.595 AC: 3058 AN: 5140

South Asian (SAS) AF: 0.520 AC: 2494 AN: 4800

European-Finnish (FIN) AF: 0.506 AC: 5340 AN: 10556

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.494 AC: 33584 AN: 67966

Other (OTH) AF: 0.567 AC: 1197 AN: 2110

Alfa AF: 0.518 Hom.: 69613

Bravo AF: 0.574

Asia WGS AF: 0.588 AC: 2043 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.023
DANN	Benign	0.35
PhyloP100		-3.0
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: rs6880837; hg19: chr5-135396669;