15-67145753-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005902.4(SMAD3):​c.207-19142A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.67 in 152,092 control chromosomes in the GnomAD database, including 36,088 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 0.67 ( 36088 hom., cov: 32)

Consequence

SMAD3
NM_005902.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.289
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]
ENSG00000259202 (HGNC:56692): (SMAD3 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.93).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SMAD3NM_005902.4 linkc.207-19142A>G intron_variant ENST00000327367.9 NP_005893.1 P84022-1A0A024R5Z3Q9P0T0

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SMAD3ENST00000327367.9 linkc.207-19142A>G intron_variant 1 NM_005902.4 ENSP00000332973.4 P84022-1

Frequencies

GnomAD3 genomes
AF:
0.670
AC:
101889
AN:
151974
Hom.:
36083
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.464
Gnomad AMI
AF:
0.763
Gnomad AMR
AF:
0.653
Gnomad ASJ
AF:
0.733
Gnomad EAS
AF:
0.387
Gnomad SAS
AF:
0.540
Gnomad FIN
AF:
0.798
Gnomad MID
AF:
0.804
Gnomad NFE
AF:
0.805
Gnomad OTH
AF:
0.688
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.670
AC:
101930
AN:
152092
Hom.:
36088
Cov.:
32
AF XY:
0.666
AC XY:
49473
AN XY:
74322
show subpopulations
Gnomad4 AFR
AF:
0.464
Gnomad4 AMR
AF:
0.652
Gnomad4 ASJ
AF:
0.733
Gnomad4 EAS
AF:
0.387
Gnomad4 SAS
AF:
0.541
Gnomad4 FIN
AF:
0.798
Gnomad4 NFE
AF:
0.805
Gnomad4 OTH
AF:
0.689
Alfa
AF:
0.775
Hom.:
58844
Bravo
AF:
0.648
Asia WGS
AF:
0.500
AC:
1741
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.93
CADD
Benign
1.9
DANN
Benign
0.71

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: rs893473; hg19: chr15-67438091; API