chr1-91683582-C-T

Position:

• chr1-91683582-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.*157G>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 0.141 in 711,200 control chromosomes in the GnomAD database, including 7,967 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 (1415 hom., cov: 32)
  • Exomes 𝑓: 0.15 (6552 hom.)
• Consequence: TGFBR3 NM_003243.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0440

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=-0.77).
• 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.*157G>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.*157G>A		3_prime_UTR_variant	17/17	1	NM_003243.5	ENSP00000212355.4

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18126 AN: 152024 Hom.: 1416 Cov.: 32

Gnomad AFR AF: 0.0316

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.113

GnomAD3 exomes AF: 0.132 AC: 17763 AN: 134990 Hom.: 1338 AF XY: 0.133 AC XY: 9753 AN XY: 73118

Gnomad AFR exome AF: 0.0246

Gnomad AMR exome AF: 0.0898

Gnomad ASJ exome AF: 0.141

Gnomad EAS exome AF: 0.114

Gnomad SAS exome AF: 0.105

Gnomad FIN exome AF: 0.160

Gnomad NFE exome AF: 0.173

Gnomad OTH exome AF: 0.133

GnomAD4 exome AF: 0.147 AC: 82388 AN: 559058 Hom.: 6552 Cov.: 6 AF XY: 0.147 AC XY: 44218 AN XY: 301628

Gnomad4 AFR exome AF: 0.0318

Gnomad4 AMR exome AF: 0.0923

Gnomad4 ASJ exome AF: 0.140

Gnomad4 EAS exome AF: 0.111

Gnomad4 SAS exome AF: 0.105

Gnomad4 FIN exome AF: 0.164

Gnomad4 NFE exome AF: 0.169

Gnomad4 OTH exome AF: 0.140

GnomAD4 genome AF: 0.119 AC: 18118 AN: 152142 Hom.: 1415 Cov.: 32 AF XY: 0.119 AC XY: 8861 AN XY: 74388

Gnomad4 AFR AF: 0.0315

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.104

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.155

Gnomad4 NFE AF: 0.169

Gnomad4 OTH AF: 0.112

Alfa AF: 0.150 Hom.: 829

Bravo AF: 0.115

Asia WGS AF: 0.0770 AC: 266 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	11
DANN	Benign	0.71
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: rs1805115; hg19: chr1-92149139;