Variant rs2229500 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_003243.5(TGFBR3):c.1341C>T(p.Ser447=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0183 in 1,614,078 control chromosomes in the GnomAD database, including 310 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.016 ( 30 hom., cov: 32)

Exomes 𝑓: 0.019 ( 280 hom. )

Consequence

TGFBR3
NM_003243.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.205

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 1-91719965-G-A is Benign according to our data. Variant chr1-91719965-G-A is described in ClinVar as [Benign]. Clinvar id is 3055456.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.205 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0157 (2390/152206) while in subpopulation NFE AF= 0.0207 (1409/68020). AF 95% confidence interval is 0.0198. There are 30 homozygotes in gnomad4. There are 1243 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2390 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGFBR3	NM_003243.5 linkuse as main transcript	c.1341C>T	p.Ser447=	synonymous_variant	9/17	ENST00000212355.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGFBR3	ENST00000212355.9 linkuse as main transcript	c.1341C>T	p.Ser447=	synonymous_variant	9/17	1	NM_003243.5	P3	Q03167-1

Frequencies

GnomAD3 genomes

AF:

0.0157

AC:

2389

AN:

152088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00427

Gnomad AMI

AF:

0.0165

Gnomad AMR

AF:

0.0202

Gnomad ASJ

AF:

0.00663

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00416

Gnomad FIN

AF:

0.0376

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0207

Gnomad OTH

AF:

0.0158

GnomAD3 exomes

AF:

0.0154

AC:

3871

AN:

251254

Hom.:

AF XY:

0.0155

AC XY:

2104

AN XY:

135778

show subpopulations

Gnomad AFR exome

AF:

0.00394

Gnomad AMR exome

AF:

0.0107

Gnomad ASJ exome

AF:

0.00764

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00451

Gnomad FIN exome

AF:

0.0397

Gnomad NFE exome

AF:

0.0197

Gnomad OTH exome

AF:

0.0214

GnomAD4 exome

AF:

0.0186

AC:

27169

AN:

1461872

Hom.:

280

Cov.:

AF XY:

0.0182

AC XY:

13241

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.00266

Gnomad4 AMR exome

AF:

0.0117

Gnomad4 ASJ exome

AF:

0.00754

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00492

Gnomad4 FIN exome

AF:

0.0403

Gnomad4 NFE exome

AF:

0.0205

Gnomad4 OTH exome

AF:

0.0157

GnomAD4 genome

AF:

0.0157

AC:

2390

AN:

152206

Hom.:

Cov.:

AF XY:

0.0167

AC XY:

1243

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.00429

Gnomad4 AMR

AF:

0.0201

Gnomad4 ASJ

AF:

0.00663

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00437

Gnomad4 FIN

AF:

0.0376

Gnomad4 NFE

AF:

0.0207

Gnomad4 OTH

AF:

0.0156

Alfa

AF:

0.0131

Hom.:

Bravo

AF:

0.0137

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.0210

EpiControl

AF:

0.0209

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

TGFBR3-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

8.7

DANN

Benign

0.56

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over