rs4324076
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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.629-16T>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 1,603,584 control chromosomes in the GnomAD database, including 200,283 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.42 ( 14761 hom., cov: 32)
Exomes 𝑓: 0.50 ( 185522 hom. )
Consequence
CYP19A1
NM_000103.4 splice_polypyrimidine_tract, intron
NM_000103.4 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.29
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=-0.73).
BP6
?
Variant 15-51218671-A-C is Benign according to our data. Variant chr15-51218671-A-C is described in ClinVar as [Benign]. Clinvar id is 1174721.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-51218671-A-C is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CYP19A1 | NM_000103.4 | c.629-16T>G | splice_polypyrimidine_tract_variant, intron_variant | ENST00000396402.6 | |||
MIR4713HG | NR_146310.1 | n.195-59312A>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CYP19A1 | ENST00000396402.6 | c.629-16T>G | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000103.4 | P1 | |||
MIR4713HG | ENST00000559909.1 | n.195-59312A>C | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.424 AC: 64466AN: 151910Hom.: 14762 Cov.: 32
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GnomAD3 exomes AF: 0.453 AC: 106346AN: 234652Hom.: 25033 AF XY: 0.459 AC XY: 58124AN XY: 126764
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GnomAD4 exome AF: 0.500 AC: 726445AN: 1451556Hom.: 185522 Cov.: 62 AF XY: 0.498 AC XY: 359067AN XY: 721224
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GnomAD4 genome ? AF: 0.424 AC: 64486AN: 152028Hom.: 14761 Cov.: 32 AF XY: 0.420 AC XY: 31242AN XY: 74324
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
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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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at