4-145540382-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_005900.3(SMAD1):​c.658+321C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 152,200 control chromosomes in the GnomAD database, including 4,873 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.17 ( 4873 hom., cov: 33)

Consequence

SMAD1
NM_005900.3 intron

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.285
Variant links:
Genes affected
SMAD1 (HGNC:6767): (SMAD family member 1) The protein encoded by this gene belongs to the SMAD, a family of proteins similar to the gene products of the Drosophila gene 'mothers against decapentaplegic' (Mad) and the C. elegans gene Sma. SMAD proteins are signal transducers and transcriptional modulators that mediate multiple signaling pathways. This protein mediates the signals of the bone morphogenetic proteins (BMPs), which are involved in a range of biological activities including cell growth, apoptosis, morphogenesis, development and immune responses. In response to BMP ligands, this protein can be phosphorylated and activated by the BMP receptor kinase. The phosphorylated form of this protein forms a complex with SMAD4, which is important for its function in the transcription regulation. This protein is a target for SMAD-specific E3 ubiquitin ligases, such as SMURF1 and SMURF2, and undergoes ubiquitination and proteasome-mediated degradation. Alternatively spliced transcript variants encoding the same protein have been observed. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
Variant 4-145540382-C-T is Benign according to our data. Variant chr4-145540382-C-T is described in ClinVar as [Benign]. Clinvar id is 1229336.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SMAD1NM_005900.3 linkc.658+321C>T intron_variant Intron 3 of 6 ENST00000302085.9 NP_005891.1 Q15797-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SMAD1ENST00000302085.9 linkc.658+321C>T intron_variant Intron 3 of 6 1 NM_005900.3 ENSP00000305769.4 Q15797-1
SMAD1ENST00000394092.6 linkc.658+321C>T intron_variant Intron 3 of 6 1 ENSP00000377652.2 Q15797-1
SMAD1ENST00000515385.1 linkc.658+321C>T intron_variant Intron 3 of 6 2 ENSP00000426568.1 Q15797-1

Frequencies

GnomAD3 genomes
AF:
0.170
AC:
25905
AN:
152082
Hom.:
4841
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.458
Gnomad AMI
AF:
0.00220
Gnomad AMR
AF:
0.133
Gnomad ASJ
AF:
0.101
Gnomad EAS
AF:
0.143
Gnomad SAS
AF:
0.179
Gnomad FIN
AF:
0.0195
Gnomad MID
AF:
0.158
Gnomad NFE
AF:
0.0353
Gnomad OTH
AF:
0.153
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.171
AC:
25990
AN:
152200
Hom.:
4873
Cov.:
33
AF XY:
0.170
AC XY:
12663
AN XY:
74408
show subpopulations
Gnomad4 AFR
AF:
0.459
Gnomad4 AMR
AF:
0.133
Gnomad4 ASJ
AF:
0.101
Gnomad4 EAS
AF:
0.142
Gnomad4 SAS
AF:
0.178
Gnomad4 FIN
AF:
0.0195
Gnomad4 NFE
AF:
0.0352
Gnomad4 OTH
AF:
0.153
Alfa
AF:
0.0584
Hom.:
1225
Bravo
AF:
0.190
Asia WGS
AF:
0.204
AC:
712
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Jul 12, 2019
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
2.9
DANN
Benign
0.66

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: rs3756021; hg19: chr4-146461534; API