chr15-67066140-G-A
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_005902.4(SMAD3):c.-15G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 1,567,362 control chromosomes in the GnomAD database, including 44,612 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_005902.4 5_prime_UTR
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SMAD3 | NM_005902.4 | c.-15G>A | 5_prime_UTR_variant | Exon 1 of 9 | ENST00000327367.9 | NP_005893.1 | ||
SMAD3 | NM_001407011.1 | c.-15G>A | 5_prime_UTR_variant | Exon 1 of 10 | NP_001393940.1 | |||
SMAD3 | NM_001407012.1 | c.-15G>A | 5_prime_UTR_variant | Exon 1 of 8 | NP_001393941.1 | |||
SMAD3 | NM_001407013.1 | c.-15G>A | 5_prime_UTR_variant | Exon 1 of 8 | NP_001393942.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SMAD3 | ENST00000327367 | c.-15G>A | 5_prime_UTR_variant | Exon 1 of 9 | 1 | NM_005902.4 | ENSP00000332973.4 | |||
SMAD3 | ENST00000560424 | c.-15G>A | 5_prime_UTR_variant | Exon 1 of 10 | 3 | ENSP00000455540.2 | ||||
SMAD3 | ENST00000559460.6 | c.-110+2196G>A | intron_variant | Intron 1 of 8 | 4 | ENSP00000453082.2 |
Frequencies
GnomAD3 genomes AF: 0.223 AC: 33775AN: 151458Hom.: 3870 Cov.: 31
GnomAD3 exomes AF: 0.232 AC: 41473AN: 178506Hom.: 5242 AF XY: 0.241 AC XY: 23287AN XY: 96594
GnomAD4 exome AF: 0.235 AC: 333285AN: 1415792Hom.: 40748 Cov.: 32 AF XY: 0.238 AC XY: 167045AN XY: 700466
GnomAD4 genome AF: 0.223 AC: 33763AN: 151570Hom.: 3864 Cov.: 31 AF XY: 0.226 AC XY: 16695AN XY: 74032
ClinVar
Submissions by phenotype
not specified Benign:4
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
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-15G>A in exon 1 of SMAD3: This variant is not expected to have clinical signifi cance because it has been identified in 22.8% (1943/8510) of European American c hromosomes from a broad population by the NHLBI Exome Sequencing Project (http:/ /evs.gs.washing -
Familial thoracic aortic aneurysm and aortic dissection Benign:2
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not provided Benign:1
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Aneurysm-osteoarthritis syndrome Benign:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at