rs1902584

Positions:

• chr15-51319457-A-T

Variant summary

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

The NM_000103.4(CYP19A1):​c.-39+19038T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0847 in 152,218 control chromosomes in the GnomAD database, including 607 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 0.085 (607 hom., cov: 32)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.283

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP19A1	NM_000103.4	c.-39+19038T>A		intron_variant		ENST00000396402.6	NP_000094.2
CYP19A1	NM_001347248.1	c.-39+4359T>A		intron_variant			NP_001334177.1
CYP19A1	NM_031226.3	c.-39+4359T>A		intron_variant			NP_112503.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP19A1	ENST00000396402.6	c.-39+19038T>A		intron_variant		1	NM_000103.4	ENSP00000379683	P1
	ENST00000559672.2	n.298-1492A>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0847 AC: 12877 AN: 152100 Hom.: 603 Cov.: 32

Gnomad AFR AF: 0.0709

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.0965

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.0512

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0790

Gnomad OTH AF: 0.0952

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

GnomAD4 genome AF: 0.0847 AC: 12893 AN: 152218 Hom.: 607 Cov.: 32 AF XY: 0.0872 AC XY: 6492 AN XY: 74424

Gnomad4 AFR AF: 0.0707

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.0965

Gnomad4 EAS AF: 0.140

Gnomad4 SAS AF: 0.205

Gnomad4 FIN AF: 0.0512

Gnomad4 NFE AF: 0.0789

Gnomad4 OTH AF: 0.0980

Alfa AF: 0.0739 Hom.: 68

Bravo AF: 0.0886

Asia WGS AF: 0.202 AC: 703 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.4
DANN	Benign	0.70

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: rs1902584; hg19: chr15-51611654;