rs12594293

Variant names:

• chr15-51231860-C-G
• rs12594293
• NM_000103.4:c.297-3927G>C

Your query was ambiguous. Multiple possible variants found:

• chr15-51231860-C-G
• chr15-51231860-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000103.4(CYP19A1):​c.297-3927G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 151,920 control chromosomes in the GnomAD database, including 2,519 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 0.14 (2519 hom., cov: 30)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.372
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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 = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP19A1	NM_000103.4	c.297-3927G>C		intron_variant	Intron 3 of 9	ENST00000396402.6	NP_000094.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP19A1	ENST00000396402.6	c.297-3927G>C		intron_variant	Intron 3 of 9	1	NM_000103.4	ENSP00000379683.1

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21165 AN: 151802 Hom.: 2512 Cov.: 30

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.0341

Gnomad AMR AF: 0.0817

Gnomad ASJ AF: 0.0796

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.0781

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0498

Gnomad OTH AF: 0.0944

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

GnomAD4 genome AF: 0.140 AC: 21209 AN: 151920 Hom.: 2519 Cov.: 30 AF XY: 0.143 AC XY: 10626 AN XY: 74224

African (AFR) AF: 0.305 AC: 12624 AN: 41374

American (AMR) AF: 0.0814 AC: 1244 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0796 AC: 276 AN: 3468

East Asian (EAS) AF: 0.252 AC: 1298 AN: 5146

South Asian (SAS) AF: 0.266 AC: 1277 AN: 4800

European-Finnish (FIN) AF: 0.0781 AC: 825 AN: 10560

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0498 AC: 3385 AN: 67976

Other (OTH) AF: 0.102 AC: 215 AN: 2108

Alfa AF: 0.0998 Hom.: 175

Bravo AF: 0.144

Asia WGS AF: 0.303 AC: 1051 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	1.2
DANN	Benign	0.37
PhyloP100		-0.37
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12594293; hg19: chr15-51524057;