rs4646
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000103.4(CYP19A1):c.*161T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.701 in 752,108 control chromosomes in the GnomAD database, including 187,141 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.70 ( 37731 hom., cov: 32)
Exomes 𝑓: 0.70 ( 149410 hom. )
Consequence
CYP19A1
NM_000103.4 3_prime_UTR
NM_000103.4 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.27
Genes affected
CYP19A1 (HGNC:2594): (cytochrome P450 family 19 subfamily A member 1) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and catalyzes the last steps of estrogen biosynthesis. Mutations in this gene can result in either increased or decreased aromatase activity; the associated phenotypes suggest that estrogen functions both as a sex steroid hormone and in growth or differentiation. Alternative promoter use and alternative splicing results in multiple transcript variants that have different tissue specificities. [provided by RefSeq, Dec 2016]
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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=-0.93).
BP6
Variant 15-51210647-A-C is Benign according to our data. Variant chr15-51210647-A-C is described in ClinVar as [Benign]. Clinvar id is 316467.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-51210647-A-C is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CYP19A1 | NM_000103.4 | c.*161T>G | 3_prime_UTR_variant | 10/10 | ENST00000396402.6 | NP_000094.2 | ||
MIR4713HG | NR_146310.1 | n.195-67336A>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CYP19A1 | ENST00000396402.6 | c.*161T>G | 3_prime_UTR_variant | 10/10 | 1 | NM_000103.4 | ENSP00000379683 | P1 | ||
CYP19A1 | ENST00000559878.5 | c.*161T>G | 3_prime_UTR_variant | 9/9 | 1 | ENSP00000453149 | P1 | |||
MIR4713HG | ENST00000559909.1 | n.195-67336A>C | intron_variant, non_coding_transcript_variant | 4 | ||||||
CYP19A1 | ENST00000396404.8 | c.*161T>G | 3_prime_UTR_variant | 11/11 | 2 | ENSP00000379685 | P1 |
Frequencies
GnomAD3 genomes AF: 0.702 AC: 106604AN: 151928Hom.: 37705 Cov.: 32
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GnomAD3 exomes AF: 0.672 AC: 147573AN: 219628Hom.: 50443 AF XY: 0.679 AC XY: 81398AN XY: 119940
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GnomAD4 exome AF: 0.701 AC: 420906AN: 600062Hom.: 149410 Cov.: 4 AF XY: 0.702 AC XY: 230169AN XY: 327918
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GnomAD4 genome AF: 0.702 AC: 106677AN: 152046Hom.: 37731 Cov.: 32 AF XY: 0.698 AC XY: 51840AN XY: 74298
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Aromatase deficiency Benign:2
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Dec 06, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | 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. - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 26, 2018 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at