1-91683282-T-C

Position:

• chr1-91683282-T-C

Variant summary

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

The NM_003243.5(TGFBR3):​c.*457A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 456,306 control chromosomes in the GnomAD database, including 4,979 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 0.13 (1535 hom., cov: 32)
  • Exomes 𝑓: 0.14 (3444 hom.)
• Consequence: TGFBR3 NM_003243.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.148

Genes affected

TGFBR3 (HGNC:11774): (transforming growth factor beta receptor 3) This locus encodes the transforming growth factor (TGF)-beta type III receptor. The encoded receptor is a membrane proteoglycan that often functions as a co-receptor with other TGF-beta receptor superfamily members. Ectodomain shedding produces soluble TGFBR3, which may inhibit TGFB signaling. Decreased expression of this receptor has been observed in various cancers. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene.[provided by RefSeq, Sep 2010]

TGFBR3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFBR3	NM_003243.5	c.*457A>G		3_prime_UTR_variant	17/17	ENST00000212355.9	NP_003234.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFBR3	ENST00000212355	c.*457A>G		3_prime_UTR_variant	17/17	1	NM_003243.5	ENSP00000212355.4

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20196 AN: 152092 Hom.: 1536 Cov.: 32

Gnomad AFR AF: 0.0754

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.124

GnomAD3 exomes AF: 0.135 AC: 18493 AN: 136558 Hom.: 1387 AF XY: 0.137 AC XY: 10124 AN XY: 74164

Gnomad AFR exome AF: 0.0716

Gnomad AMR exome AF: 0.0918

Gnomad ASJ exome AF: 0.145

Gnomad EAS exome AF: 0.120

Gnomad SAS exome AF: 0.107

Gnomad FIN exome AF: 0.158

Gnomad NFE exome AF: 0.173

Gnomad OTH exome AF: 0.133

GnomAD4 exome AF: 0.145 AC: 44067 AN: 304096 Hom.: 3444 Cov.: 0 AF XY: 0.143 AC XY: 24845 AN XY: 173192

Gnomad4 AFR exome AF: 0.0733

Gnomad4 AMR exome AF: 0.0909

Gnomad4 ASJ exome AF: 0.146

Gnomad4 EAS exome AF: 0.114

Gnomad4 SAS exome AF: 0.109

Gnomad4 FIN exome AF: 0.165

Gnomad4 NFE exome AF: 0.171

Gnomad4 OTH exome AF: 0.145

GnomAD4 genome AF: 0.133 AC: 20193 AN: 152210 Hom.: 1535 Cov.: 32 AF XY: 0.132 AC XY: 9829 AN XY: 74418

Gnomad4 AFR AF: 0.0753

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.135

Gnomad4 EAS AF: 0.109

Gnomad4 SAS AF: 0.106

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.122

Alfa AF: 0.159 Hom.: 2160

Bravo AF: 0.130

Asia WGS AF: 0.0870 AC: 304 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	13
DANN	Benign	0.72

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: rs1805117; hg19: chr1-92148839;