GeneBe

rs786205110

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 3P and 1B. PM2PP5BP4

The NM_000103.4(CYP19A1):​c.629-3C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 33)

Consequence

CYP19A1
NM_000103.4 splice_region, intron

Scores

2
Splicing: ADA: 0.9343
2

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 2.58

Publications

1 publications found
Variant links:
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]
MIR4713HG (HGNC:53124): (MIR4713 host gene)

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 15-51218658-G-T is Pathogenic according to our data. Variant chr15-51218658-G-T is described in ClinVar as Pathogenic. ClinVar VariationId is 17823.Status of the report is no_assertion_criteria_provided, 0 stars.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.49). . Strength limited to SUPPORTING due to the PP5.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000103.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
CYP19A1
NM_000103.4
MANE Select
c.629-3C>A
splice_region intron
N/ANP_000094.2
CYP19A1
NM_001347248.1
c.629-3C>A
splice_region intron
N/ANP_001334177.1P11511-1
CYP19A1
NM_001347249.2
c.629-3C>A
splice_region intron
N/ANP_001334178.1P11511-1

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
CYP19A1
ENST00000396402.6
TSL:1 MANE Select
c.629-3C>A
splice_region intron
N/AENSP00000379683.1P11511-1
CYP19A1
ENST00000559878.5
TSL:1
c.629-3C>A
splice_region intron
N/AENSP00000453149.1P11511-1
CYP19A1
ENST00000439712.6
TSL:1
n.629-3C>A
splice_region intron
N/AENSP00000390614.2E7EQ08

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
62
GnomAD4 genome
Cov.:
33

ClinVar

ClinVar submissions
Significance:Pathogenic
Revision:no assertion criteria provided
View on ClinVar
Pathogenic
VUS
Benign
Condition
1
-
-
Aromatase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.49
CADD
Benign
14
DANN
Benign
0.64
PhyloP100
2.6
Mutation Taster
=0/100
disease causing (ClinVar)

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.93
dbscSNV1_RF
Benign
0.51
SpliceAI score (max)
0.33
Details are displayed if max score is > 0.2
DS_AL_spliceai
0.33
Position offset: -3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs786205110; hg19: chr15-51510855; API