dbSNP rs1805112: TGFBR3:p.Pro402Pro (chr1-91720100-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BA1

The NM_003243.5(TGFBR3):c.1206G>A(p.Pro402Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 1,613,776 control chromosomes in the GnomAD database, including 138,302 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.39 ( 12158 hom., cov: 32)

Exomes 𝑓: 0.41 ( 126144 hom. )

Consequence

TGFBR3
NM_003243.5 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.0870

Publications

23 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 1-91720100-C-T is Benign according to our data. Variant chr1-91720100-C-T is described in ClinVar as Benign. ClinVar VariationId is 3059704.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.087 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFBR3	NM_003243.5 link	c.1206G>A	p.Pro402Pro	synonymous_variant	Exon 9 of 17	ENST00000212355.9	NP_003234.2	Q03167-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFBR3	ENST00000212355.9 link	c.1206G>A	p.Pro402Pro	synonymous_variant	Exon 9 of 17	1	NM_003243.5	ENSP00000212355.4		Q03167-1

Frequencies

GnomAD3 genomes

AF:

0.392

AC:

59534

AN:

151856

Hom.:

12157

Cov.:

show subpopulations

Gnomad AFR

AF:

0.307

Gnomad AMI

AF:

0.532

Gnomad AMR

AF:

0.346

Gnomad ASJ

AF:

0.427

Gnomad EAS

AF:

0.507

Gnomad SAS

AF:

0.449

Gnomad FIN

AF:

0.484

Gnomad MID

AF:

0.411

Gnomad NFE

AF:

0.423

Gnomad OTH

AF:

0.397

GnomAD2 exomes

AF:

0.414

AC:

103814

AN:

250966

AF XY:

0.420

show subpopulations

Gnomad AFR exome

AF:

0.305

Gnomad AMR exome

AF:

0.271

Gnomad ASJ exome

AF:

0.430

Gnomad EAS exome

AF:

0.547

Gnomad FIN exome

AF:

0.485

Gnomad NFE exome

AF:

0.431

Gnomad OTH exome

AF:

0.417

GnomAD4 exome

AF:

0.413

AC:

604454

AN:

1461802

Hom.:

126144

Cov.:

AF XY:

0.415

AC XY:

301899

AN XY:

727198

show subpopulations

African (AFR)

AF:

0.310

AC:

10390

AN:

33480

American (AMR)

AF:

0.281

AC:

12565

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.434

AC:

11335

AN:

26136

East Asian (EAS)

AF:

0.440

AC:

17475

AN:

39682

South Asian (SAS)

AF:

0.430

AC:

37122

AN:

86256

European-Finnish (FIN)

AF:

0.484

AC:

25862

AN:

53410

Middle Eastern (MID)

AF:

0.399

AC:

2295

AN:

5754

European-Non Finnish (NFE)

AF:

0.416

AC:

462569

AN:

1111970

Other (OTH)

AF:

0.411

AC:

24841

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

22639

45277

67916

90554

113193

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14198

28396

42594

56792

70990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.392

AC:

59564

AN:

151974

Hom.:

12158

Cov.:

AF XY:

0.395

AC XY:

29370

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.307

AC:

12741

AN:

41440

American (AMR)

AF:

0.345

AC:

5274

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.427

AC:

1483

AN:

3470

East Asian (EAS)

AF:

0.507

AC:

2616

AN:

5158

South Asian (SAS)

AF:

0.449

AC:

2164

AN:

4816

European-Finnish (FIN)

AF:

0.484

AC:

5105

AN:

10556

Middle Eastern (MID)

AF:

0.408

AC:

120

AN:

294

European-Non Finnish (NFE)

AF:

0.423

AC:

28745

AN:

67960

Other (OTH)

AF:

0.395

AC:

832

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1805

3611

5416

7222

9027

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

582

1164

1746

2328

2910

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.401

Hom.:

10026

Bravo

AF:

0.375

Asia WGS

AF:

0.474

AC:

1646

AN:

3478

EpiCase

AF:

0.424

EpiControl

AF:

0.424

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TGFBR3-related disorder

Benign:1

Oct 21, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

-0.40

CADD

Benign

2.3

(source)

DANN

Benign

0.54

PhyloP100

0.087

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over