Variant 1-91708703-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.2247T>C(p.Thr749=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.938 in 1,614,092 control chromosomes in the GnomAD database, including 711,345 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.94 ( 66664 hom., cov: 31)

Exomes 𝑓: 0.94 ( 644681 hom. )

Consequence

TGFBR3
NM_003243.5 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.68

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 made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 1-91708703-A-G is Benign according to our data. Variant chr1-91708703-A-G is described in ClinVar as [Benign]. Clinvar id is 3060406.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=2.68 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.935 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.2247T>C	p.Thr749=	synonymous_variant	14/17	ENST00000212355.9	NP_003234.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFBR3	ENST00000212355.9 linkuse as main transcript	c.2247T>C	p.Thr749=	synonymous_variant	14/17	1	NM_003243.5	ENSP00000212355	P3	Q03167-1

Frequencies

GnomAD3 genomes

AF:

0.935

AC:

142250

AN:

152146

Hom.:

66606

Cov.:

show subpopulations

Gnomad AFR

AF:

0.936

Gnomad AMI

AF:

0.938

Gnomad AMR

AF:

0.944

Gnomad ASJ

AF:

0.904

Gnomad EAS

AF:

0.767

Gnomad SAS

AF:

0.943

Gnomad FIN

AF:

0.969

Gnomad MID

AF:

0.896

Gnomad NFE

AF:

0.941

Gnomad OTH

AF:

0.934

GnomAD3 exomes

AF:

0.933

AC:

234439

AN:

251350

Hom.:

109695

AF XY:

0.933

AC XY:

126757

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.936

Gnomad AMR exome

AF:

0.966

Gnomad ASJ exome

AF:

0.904

Gnomad EAS exome

AF:

0.762

Gnomad SAS exome

AF:

0.947

Gnomad FIN exome

AF:

0.970

Gnomad NFE exome

AF:

0.941

Gnomad OTH exome

AF:

0.945

GnomAD4 exome

AF:

0.939

AC:

1372215

AN:

1461828

Hom.:

644681

Cov.:

AF XY:

0.939

AC XY:

682563

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.934

Gnomad4 AMR exome

AF:

0.963

Gnomad4 ASJ exome

AF:

0.904

Gnomad4 EAS exome

AF:

0.805

Gnomad4 SAS exome

AF:

0.948

Gnomad4 FIN exome

AF:

0.969

Gnomad4 NFE exome

AF:

0.942

Gnomad4 OTH exome

AF:

0.935

GnomAD4 genome

AF:

0.935

AC:

142368

AN:

152264

Hom.:

66664

Cov.:

AF XY:

0.936

AC XY:

69670

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.936

Gnomad4 AMR

AF:

0.945

Gnomad4 ASJ

AF:

0.904

Gnomad4 EAS

AF:

0.768

Gnomad4 SAS

AF:

0.943

Gnomad4 FIN

AF:

0.969

Gnomad4 NFE

AF:

0.941

Gnomad4 OTH

AF:

0.931

Alfa

AF:

0.937

Hom.:

132149

Bravo

AF:

0.933

Asia WGS

AF:

0.874

AC:

3040

AN:

3478

EpiCase

AF:

0.938

EpiControl

AF:

0.939

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 17, 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

-0.49

CADD

Benign

DANN

Benign

0.72

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