rs9972423

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

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.914

Publications

13 publications found
Variant links:
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 syndrome
    Inheritance: 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 dissection
    Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen

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=-0.65).
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
SMAD3NM_005902.4 linkc.206+33107T>A intron_variant Intron 1 of 8 ENST00000327367.9 NP_005893.1 P84022-1A0A024R5Z3Q9P0T0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SMAD3ENST00000327367.9 linkc.206+33107T>A intron_variant Intron 1 of 8 1 NM_005902.4 ENSP00000332973.4 P84022-1

Frequencies

GnomAD3 genomes
AF:
0.302
AC:
45847
AN:
152036
Hom.:
8082
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.107
Gnomad AMI
AF:
0.382
Gnomad AMR
AF:
0.325
Gnomad ASJ
AF:
0.399
Gnomad EAS
AF:
0.371
Gnomad SAS
AF:
0.430
Gnomad FIN
AF:
0.405
Gnomad MID
AF:
0.471
Gnomad NFE
AF:
0.376
Gnomad OTH
AF:
0.358
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.301
AC:
45852
AN:
152154
Hom.:
8079
Cov.:
33
AF XY:
0.307
AC XY:
22827
AN XY:
74376
show subpopulations
African (AFR)
AF:
0.107
AC:
4449
AN:
41540
American (AMR)
AF:
0.325
AC:
4967
AN:
15296
Ashkenazi Jewish (ASJ)
AF:
0.399
AC:
1384
AN:
3470
East Asian (EAS)
AF:
0.371
AC:
1924
AN:
5180
South Asian (SAS)
AF:
0.430
AC:
2068
AN:
4812
European-Finnish (FIN)
AF:
0.405
AC:
4283
AN:
10574
Middle Eastern (MID)
AF:
0.466
AC:
136
AN:
292
European-Non Finnish (NFE)
AF:
0.376
AC:
25530
AN:
67970
Other (OTH)
AF:
0.362
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:
0.244
Hom.:
747
Bravo
AF:
0.284
Asia WGS
AF:
0.406
AC:
1408
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.65
CADD
Benign
12
DANN
Benign
0.89
PhyloP100
0.91
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: rs9972423; hg19: chr15-67391805; API