15-51221725-G-C

Position:

• chr15-51221725-G-C

Variant summary

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

The ENST00000405913(CYP19A1):​c.*595C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 152,640 control chromosomes in the GnomAD database, including 14,929 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 0.43 (14843 hom., cov: 33)
  • Exomes 𝑓: 0.49 (86 hom.)
• Consequence: CYP19A1 ENST00000405913 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.331

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]

MIR4713HG (HGNC:53124): (MIR4713 host gene)

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 (NFE) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP19A1	NM_000103.4	c.628+624C>G		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+624C>G		intron_variant		1	NM_000103.4	ENSP00000379683.1

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64705 AN: 151916 Hom.: 14845 Cov.: 33

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.493

Gnomad MID AF: 0.436

Gnomad NFE AF: 0.526

Gnomad OTH AF: 0.449

GnomAD4 exome AF: 0.490 AC: 297 AN: 606 Hom.: 86 Cov.: 0 AF XY: 0.478 AC XY: 152 AN XY: 318

Gnomad4 AMR exome AF: 0.352

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.300

Gnomad4 SAS exome AF: 0.318

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.537

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.426 AC: 64721 AN: 152034 Hom.: 14843 Cov.: 33 AF XY: 0.422 AC XY: 31400 AN XY: 74342

Gnomad4 AFR AF: 0.245

Gnomad4 AMR AF: 0.371

Gnomad4 ASJ AF: 0.554

Gnomad4 EAS AF: 0.497

Gnomad4 SAS AF: 0.392

Gnomad4 FIN AF: 0.493

Gnomad4 NFE AF: 0.526

Gnomad4 OTH AF: 0.447

Alfa AF: 0.479 Hom.: 2219

Bravo AF: 0.411

Asia WGS AF: 0.384 AC: 1334 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.1
DANN	Benign	0.36

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: rs6493488; hg19: chr15-51513922;