rs284157

Positions:

• chr1-91806363-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.62-8892G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 152,036 control chromosomes in the GnomAD database, including 11,317 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 0.38 (11317 hom., cov: 32)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.493

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=-0.63).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFBR3	NM_003243.5	c.62-8892G>A		intron_variant		ENST00000212355.9	NP_003234.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFBR3	ENST00000212355.9	c.62-8892G>A		intron_variant		1	NM_003243.5	ENSP00000212355.4

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57581 AN: 151920 Hom.: 11304 Cov.: 32

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.415

Gnomad OTH AF: 0.401

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.379 AC: 57623 AN: 152036 Hom.: 11317 Cov.: 32 AF XY: 0.378 AC XY: 28109 AN XY: 74340

Gnomad4 AFR AF: 0.275

Gnomad4 AMR AF: 0.443

Gnomad4 ASJ AF: 0.448

Gnomad4 EAS AF: 0.420

Gnomad4 SAS AF: 0.438

Gnomad4 FIN AF: 0.381

Gnomad4 NFE AF: 0.415

Gnomad4 OTH AF: 0.405

Alfa AF: 0.400 Hom.: 3340

Bravo AF: 0.381

Asia WGS AF: 0.401 AC: 1392 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	12
DANN	Benign	0.73
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: rs284157; hg19: chr1-92271920;