chr1-91738246-T-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003243.5(TGFBR3):​c.385-3287A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 152,158 control chromosomes in the GnomAD database, including 17,469 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.46 ( 17469 hom., cov: 33)

Consequence

TGFBR3
NM_003243.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.04

Publications

5 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 -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TGFBR3NM_003243.5 linkc.385-3287A>G intron_variant Intron 4 of 16 ENST00000212355.9 NP_003234.2 Q03167-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TGFBR3ENST00000212355.9 linkc.385-3287A>G intron_variant Intron 4 of 16 1 NM_003243.5 ENSP00000212355.4 Q03167-1

Frequencies

GnomAD3 genomes
AF:
0.465
AC:
70709
AN:
152040
Hom.:
17450
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.289
Gnomad AMI
AF:
0.500
Gnomad AMR
AF:
0.527
Gnomad ASJ
AF:
0.450
Gnomad EAS
AF:
0.486
Gnomad SAS
AF:
0.512
Gnomad FIN
AF:
0.534
Gnomad MID
AF:
0.506
Gnomad NFE
AF:
0.542
Gnomad OTH
AF:
0.495
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.465
AC:
70746
AN:
152158
Hom.:
17469
Cov.:
33
AF XY:
0.466
AC XY:
34663
AN XY:
74390
show subpopulations
African (AFR)
AF:
0.288
AC:
11973
AN:
41512
American (AMR)
AF:
0.527
AC:
8064
AN:
15290
Ashkenazi Jewish (ASJ)
AF:
0.450
AC:
1560
AN:
3468
East Asian (EAS)
AF:
0.485
AC:
2510
AN:
5170
South Asian (SAS)
AF:
0.514
AC:
2481
AN:
4826
European-Finnish (FIN)
AF:
0.534
AC:
5656
AN:
10590
Middle Eastern (MID)
AF:
0.490
AC:
144
AN:
294
European-Non Finnish (NFE)
AF:
0.542
AC:
36851
AN:
67984
Other (OTH)
AF:
0.498
AC:
1052
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
1912
3824
5737
7649
9561
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
664
1328
1992
2656
3320
<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:
0.492
Hom.:
7728
Bravo
AF:
0.459
Asia WGS
AF:
0.469
AC:
1636
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
2.4
DANN
Benign
0.84
PhyloP100
-1.0
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs2087299; hg19: chr1-92203803; API