rs730154

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000103.4(CYP19A1):​c.-39+39488A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 152,186 control chromosomes in the GnomAD database, including 9,846 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.29 ( 9846 hom., cov: 33)

Consequence

CYP19A1
NM_000103.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.01
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CYP19A1NM_000103.4 linkuse as main transcriptc.-39+39488A>G intron_variant ENST00000396402.6 NP_000094.2
LOC124903493XR_007064634.1 linkuse as main transcriptn.3912T>C non_coding_transcript_exon_variant 1/2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CYP19A1ENST00000396402.6 linkuse as main transcriptc.-39+39488A>G intron_variant 1 NM_000103.4 ENSP00000379683 P1P11511-1

Frequencies

GnomAD3 genomes
AF:
0.294
AC:
44639
AN:
152066
Hom.:
9806
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.615
Gnomad AMI
AF:
0.127
Gnomad AMR
AF:
0.207
Gnomad ASJ
AF:
0.129
Gnomad EAS
AF:
0.321
Gnomad SAS
AF:
0.309
Gnomad FIN
AF:
0.146
Gnomad MID
AF:
0.177
Gnomad NFE
AF:
0.150
Gnomad OTH
AF:
0.245
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.294
AC:
44737
AN:
152186
Hom.:
9846
Cov.:
33
AF XY:
0.292
AC XY:
21698
AN XY:
74414
show subpopulations
Gnomad4 AFR
AF:
0.616
Gnomad4 AMR
AF:
0.207
Gnomad4 ASJ
AF:
0.129
Gnomad4 EAS
AF:
0.321
Gnomad4 SAS
AF:
0.307
Gnomad4 FIN
AF:
0.146
Gnomad4 NFE
AF:
0.150
Gnomad4 OTH
AF:
0.251
Alfa
AF:
0.229
Hom.:
1041
Bravo
AF:
0.310
Asia WGS
AF:
0.361
AC:
1258
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
0.66
DANN
Benign
0.52

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs730154; hg19: chr15-51591204; API