rs2073508

Positions:

• chr5-136047668-G-A
• chr5-136047668-G-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+248G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 496,484 control chromosomes in the GnomAD database, including 9,881 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 0.20 (3298 hom., cov: 33)
  • Exomes 𝑓: 0.19 (6583 hom.)
• Consequence: TGFBI NM_000358.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.207

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFBI	NM_000358.3	c.771+248G>A		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+248G>A		intron_variant		1	NM_000358.3	ENSP00000416330.2
TGFBI	ENST00000508767.5	c.96+248G>A		intron_variant		3		ENSP00000423871.1

Frequencies

GnomAD3 genomes AF: 0.204 AC: 31050 AN: 152110 Hom.: 3293 Cov.: 33

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.203

GnomAD4 exome AF: 0.190 AC: 65359 AN: 344256 Hom.: 6583 Cov.: 4 AF XY: 0.185 AC XY: 33124 AN XY: 179084

Gnomad4 AFR exome AF: 0.259

Gnomad4 AMR exome AF: 0.134

Gnomad4 ASJ exome AF: 0.168

Gnomad4 EAS exome AF: 0.262

Gnomad4 SAS exome AF: 0.119

Gnomad4 FIN exome AF: 0.178

Gnomad4 NFE exome AF: 0.196

Gnomad4 OTH exome AF: 0.197

GnomAD4 genome AF: 0.204 AC: 31070 AN: 152228 Hom.: 3298 Cov.: 33 AF XY: 0.200 AC XY: 14888 AN XY: 74422

Gnomad4 AFR AF: 0.265

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.175

Gnomad4 EAS AF: 0.246

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.166

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.209

Alfa AF: 0.196 Hom.: 4939

Bravo AF: 0.207

Asia WGS AF: 0.206 AC: 719 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.16

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: rs2073508; hg19: chr5-135383357;