rs284157

Variant names:

• chr1-91806363-C-T
• rs284157
• NM_003243.5:c.62-8892G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TGFBR3	NM_003243.5	c.62-8892G>A		intron_variant	Intron 2 of 16	ENST00000212355.9	NP_003234.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFBR3	ENST00000212355.9	c.62-8892G>A		intron_variant	Intron 2 of 16	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

African (AFR) AF: 0.275 AC: 11424 AN: 41470

American (AMR) AF: 0.443 AC: 6764 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 1553 AN: 3470

East Asian (EAS) AF: 0.420 AC: 2170 AN: 5166

South Asian (SAS) AF: 0.438 AC: 2112 AN: 4818

European-Finnish (FIN) AF: 0.381 AC: 4021 AN: 10554

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.415 AC: 28224 AN: 67978

Other (OTH) AF: 0.405 AC: 855 AN: 2110

Alfa AF: 0.402 Hom.: 22331

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
PhyloP100		-0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs284157; hg19: chr1-92271920;