15-51210789-G-A
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000103.4(CYP19A1):c.*19C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 1,434,492 control chromosomes in the GnomAD database, including 171,911 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_000103.4 3_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 |
---|---|---|---|---|---|---|---|---|
CYP19A1 | NM_000103.4 | c.*19C>T | 3_prime_UTR_variant | Exon 10 of 10 | ENST00000396402.6 | NP_000094.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CYP19A1 | ENST00000396402 | c.*19C>T | 3_prime_UTR_variant | Exon 10 of 10 | 1 | NM_000103.4 | ENSP00000379683.1 | |||
CYP19A1 | ENST00000559878 | c.*19C>T | 3_prime_UTR_variant | Exon 9 of 9 | 1 | ENSP00000453149.1 | ||||
CYP19A1 | ENST00000396404 | c.*19C>T | 3_prime_UTR_variant | Exon 11 of 11 | 2 | ENSP00000379685.4 | ||||
MIR4713HG | ENST00000559909.1 | n.195-67194G>A | intron_variant | Intron 1 of 2 | 4 |
Frequencies
GnomAD3 genomes AF: 0.427 AC: 64910AN: 151904Hom.: 14970 Cov.: 32
GnomAD3 exomes AF: 0.451 AC: 113281AN: 251058Hom.: 27074 AF XY: 0.455 AC XY: 61741AN XY: 135668
GnomAD4 exome AF: 0.487 AC: 624570AN: 1282470Hom.: 156938 Cov.: 19 AF XY: 0.485 AC XY: 313680AN XY: 647102
GnomAD4 genome AF: 0.427 AC: 64934AN: 152022Hom.: 14973 Cov.: 32 AF XY: 0.424 AC XY: 31526AN XY: 74284
ClinVar
Submissions by phenotype
not provided Benign:3
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This variant is associated with the following publications: (PMID: 10713674, 19879925) -
not specified Benign:2
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Aromatase deficiency 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. -
Aromatase excess syndrome Benign:1
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Letrozole response Other:1
This variant has been evaluated in 886 european women with hormone receptor-positive, early-stage breast cancer treated with adjuvant hormone therapy with letrozole. The minot T alelle was found to be associated with 1) increased cumulative incidence of distant metastasis, 2) decreased overall survival, 3) descreased cumulative incidence of bone fractures (which is a letrozole-related adverse event) likely associated with decreased letrozole efficacy
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at