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GeneBe

rs1805113

chr1-91712381-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.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 (★).

Frequency

Genomes: 𝑓 0.38 ( 11178 hom., cov: 33)
Exomes 𝑓: 0.41 ( 127519 hom. )

Consequence

TGFBR3
NM_003243.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter 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]

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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=-0.61).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 1-91712381-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 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=0.519 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
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
TGFBR3NM_003243.5 linkuse as main transcriptc.2028T>C p.Phe676= synonymous_variant 13/17 ENST00000212355.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TGFBR3ENST00000212355.9 linkuse as main transcriptc.2028T>C p.Phe676= synonymous_variant 13/171 NM_003243.5 P3Q03167-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.376
AC:
57096
AN:
151972
Hom.:
11165
Cov.:
33
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.:
52
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.376
AC:
57139
AN:
152092
Hom.:
11178
Cov.:
33
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: criteria provided, single submitter
LINK: link

Submissions by phenotype

TGFBR3-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesOct 21, 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
-0.61
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.

Other links and lift over

dbSNP: rs1805113; hg19: chr1-92177938; COSMIC: COSV53021858; COSMIC: COSV53021858; API