rs2470146

chr15-51326172-A-Gchr15-51326172-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+12323T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0482 in 152,206 control chromosomes in the GnomAD database, including 219 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 0.048 (219 hom., cov: 32)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.40

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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP19A1	NM_000103.4	c.-39+12323T>C		intron_variant		ENST00000396402.6
CYP19A1	NM_031226.3	c.-147-2248T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP19A1	ENST00000396402.6	c.-39+12323T>C		intron_variant		1	NM_000103.4	P1

Frequencies

GnomAD3 genomes AF: 0.0482 AC: 7328 AN: 152088 Hom.: 219 Cov.: 32

Gnomad AFR AF: 0.0175

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.0545

Gnomad ASJ AF: 0.0305

Gnomad EAS AF: 0.0364

Gnomad SAS AF: 0.0304

Gnomad FIN AF: 0.0693

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0646

Gnomad OTH AF: 0.0522

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

GnomAD4 genome AF: 0.0482 AC: 7330 AN: 152206 Hom.: 219 Cov.: 32 AF XY: 0.0481 AC XY: 3581 AN XY: 74406

Gnomad4 AFR AF: 0.0175

Gnomad4 AMR AF: 0.0544

Gnomad4 ASJ AF: 0.0305

Gnomad4 EAS AF: 0.0367

Gnomad4 SAS AF: 0.0311

Gnomad4 FIN AF: 0.0693

Gnomad4 NFE AF: 0.0645

Gnomad4 OTH AF: 0.0517

Alfa AF: 0.0543 Hom.: 45

Bravo AF: 0.0461

Asia WGS AF: 0.0260 AC: 89 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.072
Dann	Benign	0.43

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: rs2470146; hg19: chr15-51618369;