rs1805109

chr1-91861569-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.-38G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 1,524,980 control chromosomes in the GnomAD database, including 11,178 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 0.12 (1534 hom., cov: 32)
  • Exomes 𝑓: 0.10 (9644 hom.)
• Consequence: TGFBR3 NM_003243.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.643

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGFBR3	NM_003243.5	c.-38G>A		5_prime_UTR_variant	2/17	ENST00000212355.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGFBR3	ENST00000212355.9	c.-38G>A		5_prime_UTR_variant	2/17	1	NM_003243.5	P3

Frequencies

GnomAD3 genomes AF: 0.125 AC: 18937 AN: 152084 Hom.: 1526 Cov.: 32

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.0934

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0842

Gnomad OTH AF: 0.117

GnomAD3 exomes AF: 0.130 AC: 32576 AN: 251020 Hom.: 2922 AF XY: 0.128 AC XY: 17301 AN XY: 135682

Gnomad AFR exome AF: 0.165

Gnomad AMR exome AF: 0.125

Gnomad ASJ exome AF: 0.132

Gnomad EAS exome AF: 0.397

Gnomad SAS exome AF: 0.137

Gnomad FIN exome AF: 0.112

Gnomad NFE exome AF: 0.0854

Gnomad OTH exome AF: 0.109

GnomAD4 exome AF: 0.103 AC: 141032 AN: 1372778 Hom.: 9644 Cov.: 22 AF XY: 0.103 AC XY: 71028 AN XY: 688198

Gnomad4 AFR exome AF: 0.165

Gnomad4 AMR exome AF: 0.127

Gnomad4 ASJ exome AF: 0.136

Gnomad4 EAS exome AF: 0.418

Gnomad4 SAS exome AF: 0.136

Gnomad4 FIN exome AF: 0.110

Gnomad4 NFE exome AF: 0.0835

Gnomad4 OTH exome AF: 0.112

GnomAD4 genome AF: 0.125 AC: 18962 AN: 152202 Hom.: 1534 Cov.: 32 AF XY: 0.126 AC XY: 9394 AN XY: 74400

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.133

Gnomad4 EAS AF: 0.397

Gnomad4 SAS AF: 0.140

Gnomad4 FIN AF: 0.110

Gnomad4 NFE AF: 0.0842

Gnomad4 OTH AF: 0.123

Alfa AF: 0.0958 Hom.: 815

Bravo AF: 0.129

Asia WGS AF: 0.233 AC: 808 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	7.6
Dann	Benign	0.64
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs1805109; hg19: chr1-92327126; COSMIC: COSV53028786; COSMIC: COSV53028786;