rs12591359

Variant names:

• chr15-51247171-G-A
• rs12591359
• NM_000103.4:c.-38-4221C>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.-38-4221C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 151,802 control chromosomes in the GnomAD database, including 13,033 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 0.41 (13033 hom., cov: 31)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.570
• Publications: 16 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP19A1	NM_000103.4	c.-38-4221C>T		intron_variant	Intron 1 of 9	ENST00000396402.6	NP_000094.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP19A1	ENST00000396402.6	c.-38-4221C>T		intron_variant	Intron 1 of 9	1	NM_000103.4	ENSP00000379683.1

Frequencies

GnomAD3 genomes AF: 0.411 AC: 62376 AN: 151682 Hom.: 13027 Cov.: 31

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.602

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.429

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

GnomAD4 genome AF: 0.411 AC: 62409 AN: 151802 Hom.: 13033 Cov.: 31 AF XY: 0.416 AC XY: 30891 AN XY: 74196

African (AFR) AF: 0.354 AC: 14652 AN: 41340

American (AMR) AF: 0.448 AC: 6839 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.378 AC: 1311 AN: 3470

East Asian (EAS) AF: 0.603 AC: 3104 AN: 5148

South Asian (SAS) AF: 0.411 AC: 1978 AN: 4808

European-Finnish (FIN) AF: 0.458 AC: 4827 AN: 10540

Middle Eastern (MID) AF: 0.500 AC: 146 AN: 292

European-Non Finnish (NFE) AF: 0.416 AC: 28259 AN: 67930

Other (OTH) AF: 0.429 AC: 905 AN: 2110

Alfa AF: 0.416 Hom.: 28349

Bravo AF: 0.408

Asia WGS AF: 0.537 AC: 1868 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.4
DANN	Benign	0.39
PhyloP100		0.57
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs12591359; hg19: chr15-51539368;