rs902

Positions:

• chr1-91682670-C-G
• chr1-91682670-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.*1069G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.775 in 453,748 control chromosomes in the GnomAD database, including 137,443 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 0.79 (47878 hom., cov: 29)
  • Exomes 𝑓: 0.77 (89565 hom.)
• Consequence: TGFBR3 NM_003243.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.513

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.962 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGFBR3	NM_003243.5	c.*1069G>C		3_prime_UTR_variant	17/17	ENST00000212355.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGFBR3	ENST00000212355.9	c.*1069G>C		3_prime_UTR_variant	17/17	1	NM_003243.5	P3

Frequencies

GnomAD3 genomes AF: 0.790 AC: 119988 AN: 151834 Hom.: 47811 Cov.: 29

Gnomad AFR AF: 0.868

Gnomad AMI AF: 0.704

Gnomad AMR AF: 0.770

Gnomad ASJ AF: 0.732

Gnomad EAS AF: 0.985

Gnomad SAS AF: 0.815

Gnomad FIN AF: 0.793

Gnomad MID AF: 0.755

Gnomad NFE AF: 0.735

Gnomad OTH AF: 0.777

GnomAD3 exomes AF: 0.785 AC: 102470 AN: 130460 Hom.: 40689 AF XY: 0.784 AC XY: 55847 AN XY: 71214

Gnomad AFR exome AF: 0.875

Gnomad AMR exome AF: 0.772

Gnomad ASJ exome AF: 0.741

Gnomad EAS exome AF: 0.991

Gnomad SAS exome AF: 0.803

Gnomad FIN exome AF: 0.790

Gnomad NFE exome AF: 0.739

Gnomad OTH exome AF: 0.754

GnomAD4 exome AF: 0.767 AC: 231592 AN: 301796 Hom.: 89565 Cov.: 0 AF XY: 0.770 AC XY: 132420 AN XY: 171996

Gnomad4 AFR exome AF: 0.868

Gnomad4 AMR exome AF: 0.771

Gnomad4 ASJ exome AF: 0.743

Gnomad4 EAS exome AF: 0.991

Gnomad4 SAS exome AF: 0.803

Gnomad4 FIN exome AF: 0.778

Gnomad4 NFE exome AF: 0.736

Gnomad4 OTH exome AF: 0.765

GnomAD4 genome AF: 0.790 AC: 120112 AN: 151952 Hom.: 47878 Cov.: 29 AF XY: 0.794 AC XY: 58996 AN XY: 74256

Gnomad4 AFR AF: 0.868

Gnomad4 AMR AF: 0.770

Gnomad4 ASJ AF: 0.732

Gnomad4 EAS AF: 0.985

Gnomad4 SAS AF: 0.815

Gnomad4 FIN AF: 0.793

Gnomad4 NFE AF: 0.736

Gnomad4 OTH AF: 0.779

Alfa AF: 0.756 Hom.: 7730

Bravo AF: 0.792

Asia WGS AF: 0.891 AC: 3102 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.50
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: rs902; hg19: chr1-92148227;