rs9972423
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_005902.4(SMAD3):c.206+33107T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 152,154 control chromosomes in the GnomAD database, including 8,079 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 0.30 ( 8079 hom., cov: 33)
Consequence
SMAD3
NM_005902.4 intron
NM_005902.4 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.914
Publications
13 publications found
Genes affected
SMAD3 (HGNC:6769): (SMAD family member 3) The SMAD family of proteins are a group of intracellular signal transducer proteins similar to the gene products of the Drosophila gene 'mothers against decapentaplegic' (Mad) and the C. elegans gene Sma. The SMAD3 protein functions in the transforming growth factor-beta signaling pathway, and transmits signals from the cell surface to the nucleus, regulating gene activity and cell proliferation. This protein forms a complex with other SMAD proteins and binds DNA, functioning both as a transcription factor and tumor suppressor. Mutations in this gene are associated with aneurysms-osteoarthritis syndrome and Loeys-Dietz Syndrome 3. [provided by RefSeq, May 2022]
SMAD3 Gene-Disease associations (from GenCC):
- aneurysm-osteoarthritis syndromeInheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Genomics England PanelApp, Orphanet, G2P, ClinGen, Labcorp Genetics (formerly Invitae)
- familial thoracic aortic aneurysm and aortic dissectionInheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
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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=-0.65).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SMAD3 | NM_005902.4 | c.206+33107T>A | intron_variant | Intron 1 of 8 | ENST00000327367.9 | NP_005893.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.302 AC: 45847AN: 152036Hom.: 8082 Cov.: 33 show subpopulations
GnomAD3 genomes
AF:
AC:
45847
AN:
152036
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome AF: 0.301 AC: 45852AN: 152154Hom.: 8079 Cov.: 33 AF XY: 0.307 AC XY: 22827AN XY: 74376 show subpopulations
GnomAD4 genome
AF:
AC:
45852
AN:
152154
Hom.:
Cov.:
33
AF XY:
AC XY:
22827
AN XY:
74376
show subpopulations
African (AFR)
AF:
AC:
4449
AN:
41540
American (AMR)
AF:
AC:
4967
AN:
15296
Ashkenazi Jewish (ASJ)
AF:
AC:
1384
AN:
3470
East Asian (EAS)
AF:
AC:
1924
AN:
5180
South Asian (SAS)
AF:
AC:
2068
AN:
4812
European-Finnish (FIN)
AF:
AC:
4283
AN:
10574
Middle Eastern (MID)
AF:
AC:
136
AN:
292
European-Non Finnish (NFE)
AF:
AC:
25530
AN:
67970
Other (OTH)
AF:
AC:
763
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
1573
3147
4720
6294
7867
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Genome Hom
Variant carriers
0
482
964
1446
1928
2410
<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:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
1408
AN:
3478
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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