rs730154

chr15-51299007-T-C

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.01

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]

LOC124903493 (HGNC:):

ACMG classification

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	UniProt
CYP19A1	NM_000103.4	c.-39+39488A>G		intron_variant		ENST00000396402.6
LOC124903493	XR_007064634.1	n.3912T>C		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP19A1	ENST00000396402.6	c.-39+39488A>G		intron_variant		1	NM_000103.4	P1

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44639 AN: 152066 Hom.: 9806 Cov.: 33

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

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

Other links and lift over

dbSNP: rs730154; hg19: chr15-51591204;