rs6700529

Positions:

• chr1-91770785-C-A
• chr1-91770785-C-G

Variant summary

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

The NM_003243.5(TGFBR3):​c.247-12035G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,112 control chromosomes in the GnomAD database, including 1,398 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 (1398 hom., cov: 32)
  • Exomes 𝑓: 0.17 (0 hom.)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0520

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]

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 = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGFBR3	NM_003243.5	c.247-12035G>T		intron_variant		ENST00000212355.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGFBR3	ENST00000212355.9	c.247-12035G>T		intron_variant		1	NM_003243.5	P3

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19187 AN: 151988 Hom.: 1377 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.0418

Gnomad SAS AF: 0.0724

Gnomad FIN AF: 0.0852

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.131

GnomAD4 exome AF: 0.167 AC: 1 AN: 6 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

Gnomad4 NFE exome AF: 0.167

GnomAD4 genome AF: 0.127 AC: 19257 AN: 152106 Hom.: 1398 Cov.: 32 AF XY: 0.124 AC XY: 9239 AN XY: 74358

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.0417

Gnomad4 SAS AF: 0.0731

Gnomad4 FIN AF: 0.0852

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.130

Alfa AF: 0.0890 Hom.: 235

Bravo AF: 0.134

Asia WGS AF: 0.0840 AC: 293 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	0.88
DANN	Benign	0.37

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: rs6700529; hg19: chr1-92236342;