Variant chr1-91712381-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_003243.5(TGFBR3):c.2028T>C(p.Phe676=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 1,613,752 control chromosomes in the GnomAD database, including 138,697 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.38 ( 11178 hom., cov: 33)

Exomes 𝑓: 0.41 ( 127519 hom. )

Consequence

TGFBR3
NM_003243.5 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.519

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 1-91712381-A-G is Benign according to our data. Variant chr1-91712381-A-G is described in ClinVar as [Benign]. Clinvar id is 3059465.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.519 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGFBR3	NM_003243.5 linkuse as main transcript	c.2028T>C	p.Phe676=	synonymous_variant	13/17	ENST00000212355.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGFBR3	ENST00000212355.9 linkuse as main transcript	c.2028T>C	p.Phe676=	synonymous_variant	13/17	1	NM_003243.5	P3	Q03167-1

Frequencies

GnomAD3 genomes

AF:

0.376

AC:

57096

AN:

151972

Hom.:

11165

Cov.:

show subpopulations

Gnomad AFR

AF:

0.342

Gnomad AMI

AF:

0.495

Gnomad AMR

AF:

0.328

Gnomad ASJ

AF:

0.347

Gnomad EAS

AF:

0.0885

Gnomad SAS

AF:

0.277

Gnomad FIN

AF:

0.349

Gnomad MID

AF:

0.341

Gnomad NFE

AF:

0.440

Gnomad OTH

AF:

0.361

GnomAD3 exomes

AF:

0.359

AC:

90265

AN:

251288

Hom.:

17714

AF XY:

0.362

AC XY:

49156

AN XY:

135798

show subpopulations

Gnomad AFR exome

AF:

0.336

Gnomad AMR exome

AF:

0.288

Gnomad ASJ exome

AF:

0.341

Gnomad EAS exome

AF:

0.104

Gnomad SAS exome

AF:

0.288

Gnomad FIN exome

AF:

0.359

Gnomad NFE exome

AF:

0.445

Gnomad OTH exome

AF:

0.385

GnomAD4 exome

AF:

0.410

AC:

599306

AN:

1461660

Hom.:

127519

Cov.:

AF XY:

0.407

AC XY:

296011

AN XY:

727150

show subpopulations

Gnomad4 AFR exome

AF:

0.337

Gnomad4 AMR exome

AF:

0.291

Gnomad4 ASJ exome

AF:

0.343

Gnomad4 EAS exome

AF:

0.0903

Gnomad4 SAS exome

AF:

0.290

Gnomad4 FIN exome

AF:

0.370

Gnomad4 NFE exome

AF:

0.443

Gnomad4 OTH exome

AF:

0.383

GnomAD4 genome

AF:

0.376

AC:

57139

AN:

152092

Hom.:

11178

Cov.:

AF XY:

0.366

AC XY:

27229

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.343

Gnomad4 AMR

AF:

0.327

Gnomad4 ASJ

AF:

0.347

Gnomad4 EAS

AF:

0.0887

Gnomad4 SAS

AF:

0.276

Gnomad4 FIN

AF:

0.349

Gnomad4 NFE

AF:

0.440

Gnomad4 OTH

AF:

0.359

Alfa

AF:

0.422

Hom.:

32728

Bravo

AF:

0.375

Asia WGS

AF:

0.210

AC:

729

AN:

3478

EpiCase

AF:

0.440

EpiControl

AF:

0.442

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

-0.61

CADD

Benign

6.7

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