rs200726236
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_005585.5(SMAD6):c.817+9G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000405 in 1,460,496 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0023 ( 2 hom., cov: 33)
Exomes 𝑓: 0.00019 ( 1 hom. )
Consequence
SMAD6
NM_005585.5 intron
NM_005585.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.60
Genes affected
SMAD6 (HGNC:6772): (SMAD family member 6) The protein encoded by this gene belongs to the SMAD family of proteins, which are related to Drosophila 'mothers against decapentaplegic' (Mad) and C. elegans Sma. SMAD proteins are signal transducers and transcriptional modulators that mediate multiple signaling pathways. This protein functions in the negative regulation of BMP and TGF-beta/activin-signalling. Multiple transcript variants have been found for this gene.[provided by RefSeq, Sep 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.6).
BP6
?
Variant 15-66704084-G-C is Benign according to our data. Variant chr15-66704084-G-C is described in ClinVar as [Benign]. Clinvar id is 240181.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00226 (344/152308) while in subpopulation AFR AF= 0.00786 (327/41582). AF 95% confidence interval is 0.00716. There are 2 homozygotes in gnomad4. There are 152 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 344 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMAD6 | NM_005585.5 | c.817+9G>C | intron_variant | ENST00000288840.10 | |||
SMAD6 | NR_027654.2 | n.1840+9G>C | intron_variant, non_coding_transcript_variant | ||||
SMAD6 | XR_931827.3 | n.1840+9G>C | intron_variant, non_coding_transcript_variant | ||||
SMAD6 | XM_011521561.3 | upstream_gene_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMAD6 | ENST00000288840.10 | c.817+9G>C | intron_variant | 1 | NM_005585.5 | P1 | |||
SMAD6 | ENST00000557916.5 | c.817+9G>C | intron_variant, NMD_transcript_variant | 1 | |||||
SMAD6 | ENST00000612349.1 | n.1008G>C | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes ? AF: 0.00226 AC: 344AN: 152192Hom.: 2 Cov.: 33
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GnomAD3 exomes AF: 0.000266 AC: 19AN: 71490Hom.: 0 AF XY: 0.000118 AC XY: 5AN XY: 42552
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GnomAD4 exome AF: 0.000189 AC: 247AN: 1308188Hom.: 1 Cov.: 30 AF XY: 0.000152 AC XY: 98AN XY: 646216
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GnomAD4 genome ? AF: 0.00226 AC: 344AN: 152308Hom.: 2 Cov.: 33 AF XY: 0.00204 AC XY: 152AN XY: 74470
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
SMAD6-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 03, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Aortic valve disease 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at