1-91682456-C-T

Position:

• chr1-91682456-C-T

Variant summary

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

The NM_003243.5(TGFBR3):​c.*1283G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 439,832 control chromosomes in the GnomAD database, including 7,048 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 0.18 (2557 hom., cov: 25)
  • Exomes 𝑓: 0.16 (4491 hom.)
• Consequence: TGFBR3 NM_003243.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.227

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=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFBR3	NM_003243.5	c.*1283G>A		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	ENST00000212355.9	c.*1283G>A		3_prime_UTR_variant	17/17	1	NM_003243.5	ENSP00000212355.4

Frequencies

GnomAD3 genomes AF: 0.182 AC: 25189 AN: 138614 Hom.: 2553 Cov.: 25

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.0830

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.0940

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.194

GnomAD3 exomes AF: 0.180 AC: 23355 AN: 130108 Hom.: 2689 AF XY: 0.170 AC XY: 12084 AN XY: 71004

Gnomad AFR exome AF: 0.182

Gnomad AMR exome AF: 0.249

Gnomad ASJ exome AF: 0.109

Gnomad EAS exome AF: 0.414

Gnomad SAS exome AF: 0.0837

Gnomad FIN exome AF: 0.274

Gnomad NFE exome AF: 0.141

Gnomad OTH exome AF: 0.169

GnomAD4 exome AF: 0.156 AC: 46887 AN: 301160 Hom.: 4491 Cov.: 0 AF XY: 0.147 AC XY: 25231 AN XY: 171538

Gnomad4 AFR exome AF: 0.179

Gnomad4 AMR exome AF: 0.248

Gnomad4 ASJ exome AF: 0.109

Gnomad4 EAS exome AF: 0.426

Gnomad4 SAS exome AF: 0.0861

Gnomad4 FIN exome AF: 0.255

Gnomad4 NFE exome AF: 0.144

Gnomad4 OTH exome AF: 0.161

GnomAD4 genome AF: 0.182 AC: 25199 AN: 138672 Hom.: 2557 Cov.: 25 AF XY: 0.190 AC XY: 12612 AN XY: 66500

Gnomad4 AFR AF: 0.190

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.443

Gnomad4 SAS AF: 0.0938

Gnomad4 FIN AF: 0.292

Gnomad4 NFE AF: 0.146

Gnomad4 OTH AF: 0.197

Alfa AF: 0.146 Hom.: 2308

Bravo AF: 0.178

Asia WGS AF: 0.257 AC: 895 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	8.7
DANN	Benign	0.61

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: rs1804506; hg19: chr1-92148013;