Variant 1-91720100-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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:

TGFBR3 (HGNC:):

TGFBR3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
TGFBR3	NM_003243.5 linkuse as main transcript	c.1206G>A	p.Pro402Pro	synonymous_variant	9/17	ENST00000212355.9	NP_003234.2	Q03167-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFBR3	ENST00000212355.9 linkuse as main transcript	c.1206G>A	p.Pro402Pro	synonymous_variant	9/17	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

GnomAD3 exomes

AF:

0.414

AC:

103814

AN:

250966

Hom.:

22350

AF XY:

0.420

AC XY:

56930

AN XY:

135624

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 SAS exome

AF:

0.433

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

Gnomad4 AFR exome

AF:

0.310

Gnomad4 AMR exome

AF:

0.281

Gnomad4 ASJ exome

AF:

0.434

Gnomad4 EAS exome

AF:

0.440

Gnomad4 SAS exome

AF:

0.430

Gnomad4 FIN exome

AF:

0.484

Gnomad4 NFE exome

AF:

0.416

Gnomad4 OTH exome

AF:

0.411

GnomAD4 genome

AF:

0.392

AC:

59564

AN:

151974

Hom.:

12158

Cov.:

AF XY:

0.395

AC XY:

29370

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.307

Gnomad4 AMR

AF:

0.345

Gnomad4 ASJ

AF:

0.427

Gnomad4 EAS

AF:

0.507

Gnomad4 SAS

AF:

0.449

Gnomad4 FIN

AF:

0.484

Gnomad4 NFE

AF:

0.423

Gnomad4 OTH

AF:

0.395

Alfa

AF:

0.403

Hom.:

9080

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

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 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

-0.40

CADD

Benign

2.3

DANN

Benign

0.54

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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