chr1-91719965-G-A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_003243.5(TGFBR3):​c.1341C>T​(p.Ser447Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0183 in 1,614,078 control chromosomes in the GnomAD database, including 310 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.016 ( 30 hom., cov: 32)
Exomes 𝑓: 0.019 ( 280 hom. )

Consequence

TGFBR3
NM_003243.5 synonymous

Scores

2

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.205

Publications

3 publications found
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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.68).
BP6
Variant 1-91719965-G-A is Benign according to our data. Variant chr1-91719965-G-A is described in CliVar as Benign. Clinvar id is 3055456.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-91719965-G-A is described in CliVar as Benign. Clinvar id is 3055456.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-91719965-G-A is described in CliVar as Benign. Clinvar id is 3055456.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-91719965-G-A is described in CliVar as Benign. Clinvar id is 3055456.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-91719965-G-A is described in CliVar as Benign. Clinvar id is 3055456.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-91719965-G-A is described in CliVar as Benign. Clinvar id is 3055456.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-91719965-G-A is described in CliVar as Benign. Clinvar id is 3055456.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-91719965-G-A is described in CliVar as Benign. Clinvar id is 3055456.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-91719965-G-A is described in CliVar as Benign. Clinvar id is 3055456.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-91719965-G-A is described in CliVar as Benign. Clinvar id is 3055456.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-91719965-G-A is described in CliVar as Benign. Clinvar id is 3055456.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-91719965-G-A is described in CliVar as Benign. Clinvar id is 3055456.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-91719965-G-A is described in CliVar as Benign. Clinvar id is 3055456.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-91719965-G-A is described in CliVar as Benign. Clinvar id is 3055456.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-91719965-G-A is described in CliVar as Benign. Clinvar id is 3055456.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-91719965-G-A is described in CliVar as Benign. Clinvar id is 3055456.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-91719965-G-A is described in CliVar as Benign. Clinvar id is 3055456.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-91719965-G-A is described in CliVar as Benign. Clinvar id is 3055456.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-91719965-G-A is described in CliVar as Benign. Clinvar id is 3055456.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-91719965-G-A is described in CliVar as Benign. Clinvar id is 3055456.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-91719965-G-A is described in CliVar as Benign. Clinvar id is 3055456.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-91719965-G-A is described in CliVar as Benign. Clinvar id is 3055456.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-91719965-G-A is described in CliVar as Benign. Clinvar id is 3055456.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-91719965-G-A is described in CliVar as Benign. Clinvar id is 3055456.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-91719965-G-A is described in CliVar as Benign. Clinvar id is 3055456.Status of the report is no_assertion_criteria_provided, 0 stars.
BP7
Synonymous conserved (PhyloP=0.205 with no splicing effect.
BS1
Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0157 (2390/152206) while in subpopulation NFE AF = 0.0207 (1409/68020). AF 95% confidence interval is 0.0198. There are 30 homozygotes in GnomAd4. There are 1243 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
BS2
High AC in GnomAd4 at 2390 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TGFBR3NM_003243.5 linkc.1341C>T p.Ser447Ser synonymous_variant Exon 9 of 17 ENST00000212355.9 NP_003234.2 Q03167-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TGFBR3ENST00000212355.9 linkc.1341C>T p.Ser447Ser synonymous_variant Exon 9 of 17 1 NM_003243.5 ENSP00000212355.4 Q03167-1

Frequencies

GnomAD3 genomes
AF:
0.0157
AC:
2389
AN:
152088
Hom.:
30
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00427
Gnomad AMI
AF:
0.0165
Gnomad AMR
AF:
0.0202
Gnomad ASJ
AF:
0.00663
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00416
Gnomad FIN
AF:
0.0376
Gnomad MID
AF:
0.00949
Gnomad NFE
AF:
0.0207
Gnomad OTH
AF:
0.0158
GnomAD2 exomes
AF:
0.0154
AC:
3871
AN:
251254
AF XY:
0.0155
show subpopulations
Gnomad AFR exome
AF:
0.00394
Gnomad AMR exome
AF:
0.0107
Gnomad ASJ exome
AF:
0.00764
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0397
Gnomad NFE exome
AF:
0.0197
Gnomad OTH exome
AF:
0.0214
GnomAD4 exome
AF:
0.0186
AC:
27169
AN:
1461872
Hom.:
280
Cov.:
32
AF XY:
0.0182
AC XY:
13241
AN XY:
727234
show subpopulations
African (AFR)
AF:
0.00266
AC:
89
AN:
33480
American (AMR)
AF:
0.0117
AC:
522
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00754
AC:
197
AN:
26136
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.00492
AC:
424
AN:
86256
European-Finnish (FIN)
AF:
0.0403
AC:
2153
AN:
53418
Middle Eastern (MID)
AF:
0.0163
AC:
94
AN:
5766
European-Non Finnish (NFE)
AF:
0.0205
AC:
22742
AN:
1111996
Other (OTH)
AF:
0.0157
AC:
948
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.472
Heterozygous variant carriers
0
1571
3142
4714
6285
7856
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
822
1644
2466
3288
4110
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0157
AC:
2390
AN:
152206
Hom.:
30
Cov.:
32
AF XY:
0.0167
AC XY:
1243
AN XY:
74408
show subpopulations
African (AFR)
AF:
0.00429
AC:
178
AN:
41532
American (AMR)
AF:
0.0201
AC:
308
AN:
15286
Ashkenazi Jewish (ASJ)
AF:
0.00663
AC:
23
AN:
3470
East Asian (EAS)
AF:
0.000193
AC:
1
AN:
5174
South Asian (SAS)
AF:
0.00437
AC:
21
AN:
4808
European-Finnish (FIN)
AF:
0.0376
AC:
399
AN:
10600
Middle Eastern (MID)
AF:
0.0102
AC:
3
AN:
294
European-Non Finnish (NFE)
AF:
0.0207
AC:
1409
AN:
68020
Other (OTH)
AF:
0.0156
AC:
33
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.492
Heterozygous variant carriers
0
108
217
325
434
542
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
26
52
78
104
130
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0131
Hom.:
15
Bravo
AF:
0.0137
Asia WGS
AF:
0.00346
AC:
12
AN:
3478
EpiCase
AF:
0.0210
EpiControl
AF:
0.0209

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

TGFBR3-related disorder Benign:1
Feb 21, 2019
PreventionGenetics, part of Exact Sciences
Significance:Benign
Review Status:no assertion criteria provided
Collection Method:clinical testing

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
-0.68
CADD
Benign
8.7
DANN
Benign
0.56
PhyloP100
0.20
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Mutation Taster
=100/0
polymorphism (auto)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs2229500; hg19: chr1-92185522; API