15-51324283-G-A

Position:

• chr15-51324283-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000103.4(CYP19A1):​c.-39+14212C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,218 control chromosomes in the GnomAD database, including 2,904 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 0.19 (2904 hom., cov: 32)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.778

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP19A1	NM_000103.4	c.-39+14212C>T		intron_variant		ENST00000396402.6
CYP19A1	NM_031226.3	c.-147-359C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP19A1	ENST00000396402.6	c.-39+14212C>T		intron_variant		1	NM_000103.4	P1

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28303 AN: 152100 Hom.: 2907 Cov.: 32

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.0152

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.199

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.186 AC: 28310 AN: 152218 Hom.: 2904 Cov.: 32 AF XY: 0.184 AC XY: 13663 AN XY: 74418

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.263

Gnomad4 ASJ AF: 0.234

Gnomad4 EAS AF: 0.0152

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.133

Gnomad4 NFE AF: 0.210

Gnomad4 OTH AF: 0.197

Alfa AF: 0.214 Hom.: 3681

Bravo AF: 0.197

Asia WGS AF: 0.0970 AC: 336 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.32
DANN	Benign	0.31

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

Other links and lift over

dbSNP: rs4774585; hg19: chr15-51616480;