rs17601241
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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.858+26C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0929 in 1,613,754 control chromosomes in the GnomAD database, including 8,049 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.086 ( 710 hom., cov: 33)
Exomes 𝑓: 0.094 ( 7339 hom. )
Consequence
CYP19A1
NM_000103.4 intron
NM_000103.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.104
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=-0.84).
BP6
Variant 15-51215677-G-A is Benign according to our data. Variant chr15-51215677-G-A is described in ClinVar as [Benign]. Clinvar id is 1293221.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CYP19A1 | NM_000103.4 | c.858+26C>T | intron_variant | ENST00000396402.6 | NP_000094.2 | |||
MIR4713HG | NR_146310.1 | n.195-62306G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CYP19A1 | ENST00000396402.6 | c.858+26C>T | intron_variant | 1 | NM_000103.4 | ENSP00000379683 | P1 | |||
MIR4713HG | ENST00000559909.1 | n.195-62306G>A | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes AF: 0.0864 AC: 13135AN: 152090Hom.: 711 Cov.: 33
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GnomAD3 exomes AF: 0.106 AC: 26610AN: 251074Hom.: 1857 AF XY: 0.105 AC XY: 14195AN XY: 135714
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GnomAD4 exome AF: 0.0936 AC: 136761AN: 1461546Hom.: 7339 Cov.: 35 AF XY: 0.0945 AC XY: 68707AN XY: 727066
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GnomAD4 genome AF: 0.0863 AC: 13134AN: 152208Hom.: 710 Cov.: 33 AF XY: 0.0898 AC XY: 6686AN XY: 74414
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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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