rs2118611

Variant summary

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

The NM_005902.4(SMAD3):​c.206+42768T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 152,184 control chromosomes in the GnomAD database, including 4,845 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 0.24 ( 4845 hom., cov: 33)

Consequence

SMAD3
NM_005902.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.215
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SMAD3NM_005902.4 linkuse as main transcriptc.206+42768T>C intron_variant ENST00000327367.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SMAD3ENST00000327367.9 linkuse as main transcriptc.206+42768T>C intron_variant 1 NM_005902.4 P1P84022-1

Frequencies

GnomAD3 genomes
AF:
0.237
AC:
36098
AN:
152066
Hom.:
4836
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.216
Gnomad AMI
AF:
0.194
Gnomad AMR
AF:
0.344
Gnomad ASJ
AF:
0.278
Gnomad EAS
AF:
0.528
Gnomad SAS
AF:
0.355
Gnomad FIN
AF:
0.199
Gnomad MID
AF:
0.120
Gnomad NFE
AF:
0.201
Gnomad OTH
AF:
0.251
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.237
AC:
36123
AN:
152184
Hom.:
4845
Cov.:
33
AF XY:
0.244
AC XY:
18182
AN XY:
74404
show subpopulations
Gnomad4 AFR
AF:
0.216
Gnomad4 AMR
AF:
0.345
Gnomad4 ASJ
AF:
0.278
Gnomad4 EAS
AF:
0.527
Gnomad4 SAS
AF:
0.354
Gnomad4 FIN
AF:
0.199
Gnomad4 NFE
AF:
0.201
Gnomad4 OTH
AF:
0.250
Alfa
AF:
0.243
Hom.:
891
Bravo
AF:
0.250
Asia WGS
AF:
0.399
AC:
1385
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
6.5
DANN
Benign
0.59

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: rs2118611; hg19: chr15-67401466; API