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GeneBe

1-91708703-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

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 (★).

Frequency

Genomes: 𝑓 0.94 ( 66664 hom., cov: 31)
Exomes 𝑓: 0.94 ( 644681 hom. )

Consequence

TGFBR3
NM_003243.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter 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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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 criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=2.68 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
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 UniProt
TGFBR3NM_003243.5 linkuse as main transcriptc.2247T>C p.Thr749= synonymous_variant 14/17 ENST00000212355.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TGFBR3ENST00000212355.9 linkuse as main transcriptc.2247T>C p.Thr749= synonymous_variant 14/171 NM_003243.5 P3Q03167-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.935
AC:
142250
AN:
152146
Hom.:
66606
Cov.:
31
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.:
66
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.935
AC:
142368
AN:
152264
Hom.:
66664
Cov.:
31
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: criteria provided, single submitter
LINK: link

Submissions by phenotype

TGFBR3-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesOct 17, 2019This 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
10
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.

Other links and lift over

dbSNP: rs284878; hg19: chr1-92174260; API