chr1-91683720-C-T

Variant names:

• chr1-91683720-C-T
• rs1131243
• NM_003243.5:c.*19G>A

Variant summary

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

The NM_003243.5(TGFBR3):​c.*19G>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 0.17 in 1,406,694 control chromosomes in the GnomAD database, including 19,366 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 0.14 (1601 hom., cov: 32)
  • Exomes 𝑓: 0.17 (17765 hom.)
• Consequence: TGFBR3 NM_003243.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.122

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=-0.49).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFBR3	NM_003243.5	c.*19G>A		3_prime_UTR_variant	Exon 17 of 17	ENST00000212355.9	NP_003234.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFBR3	ENST00000212355	c.*19G>A		3_prime_UTR_variant	Exon 17 of 17	1	NM_003243.5	ENSP00000212355.4

Frequencies

GnomAD3 genomes AF: 0.143 AC: 20695 AN: 145188 Hom.: 1597 Cov.: 32

Gnomad AFR AF: 0.0907

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.163

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.128

GnomAD3 exomes AF: 0.135 AC: 20295 AN: 150396 Hom.: 1496 AF XY: 0.136 AC XY: 10892 AN XY: 80192

Gnomad AFR exome AF: 0.0807

Gnomad AMR exome AF: 0.0920

Gnomad ASJ exome AF: 0.145

Gnomad EAS exome AF: 0.117

Gnomad SAS exome AF: 0.106

Gnomad FIN exome AF: 0.153

Gnomad NFE exome AF: 0.171

Gnomad OTH exome AF: 0.135

GnomAD4 exome AF: 0.173 AC: 218654 AN: 1261374 Hom.: 17765 Cov.: 31 AF XY: 0.173 AC XY: 107550 AN XY: 621954

Gnomad4 AFR exome AF: 0.0960

Gnomad4 AMR exome AF: 0.107

Gnomad4 ASJ exome AF: 0.179

Gnomad4 EAS exome AF: 0.161

Gnomad4 SAS exome AF: 0.110

Gnomad4 FIN exome AF: 0.226

Gnomad4 NFE exome AF: 0.181

Gnomad4 OTH exome AF: 0.170

GnomAD4 genome AF: 0.143 AC: 20713 AN: 145320 Hom.: 1601 Cov.: 32 AF XY: 0.142 AC XY: 10077 AN XY: 70826

Gnomad4 AFR AF: 0.0912

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.173

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.127

Alfa AF: 0.106 Hom.: 216

Bravo AF: 0.134

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	5.3
DANN	Benign	0.88
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1131243; hg19: chr1-92149277;