rs6493487

Positions:

• chr15-51221532-G-A
• chr15-51221532-G-C
• chr15-51221532-G-T

Variant summary

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

The ENST00000405913(CYP19A1):​c.*788C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.79 in 152,142 control chromosomes in the GnomAD database, including 47,977 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 0.79 (47976 hom., cov: 33)
  • Exomes 𝑓: 1.0 (1 hom.)
• Consequence: CYP19A1 ENST00000405913 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.539

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]

CYP19A1 (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 (AFR) allele frequency at 95% confidence interval = 0.906 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP19A1	NM_000103.4	c.628+817C>T		intron_variant		ENST00000396402.6	NP_000094.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP19A1	ENST00000396402.6	c.628+817C>T		intron_variant		1	NM_000103.4	ENSP00000379683.1

Frequencies

GnomAD3 genomes AF: 0.790 AC: 120140 AN: 152022 Hom.: 47928 Cov.: 33

Gnomad AFR AF: 0.914

Gnomad AMI AF: 0.770

Gnomad AMR AF: 0.699

Gnomad ASJ AF: 0.736

Gnomad EAS AF: 0.694

Gnomad SAS AF: 0.792

Gnomad FIN AF: 0.787

Gnomad MID AF: 0.637

Gnomad NFE AF: 0.748

Gnomad OTH AF: 0.746

GnomAD4 exome AF: 1.00 AC: 2 AN: 2 Hom.: 1 Cov.: 0 AF XY: 1.00 AC XY: 2 AN XY: 2

Gnomad4 FIN exome AF: 1.00

GnomAD4 genome AF: 0.790 AC: 120239 AN: 152140 Hom.: 47976 Cov.: 33 AF XY: 0.790 AC XY: 58768 AN XY: 74364

Gnomad4 AFR AF: 0.914

Gnomad4 AMR AF: 0.698

Gnomad4 ASJ AF: 0.736

Gnomad4 EAS AF: 0.694

Gnomad4 SAS AF: 0.792

Gnomad4 FIN AF: 0.787

Gnomad4 NFE AF: 0.748

Gnomad4 OTH AF: 0.745

Alfa AF: 0.775 Hom.: 10134

Bravo AF: 0.786

Asia WGS AF: 0.725 AC: 2519 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.2
DANN	Benign	0.62

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: rs6493487; hg19: chr15-51513729;