rs12439137

Variant names:

• chr15-51224107-A-G
• rs12439137
• NM_000103.4:c.452-1582T>C

Variant summary

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

The NM_000103.4(CYP19A1):​c.452-1582T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 152,184 control chromosomes in the GnomAD database, including 974 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 0.10 (974 hom., cov: 32)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51
• Publications: 12 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP19A1	NM_000103.4	c.452-1582T>C		intron_variant	Intron 4 of 9	ENST00000396402.6	NP_000094.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP19A1	ENST00000396402.6	c.452-1582T>C		intron_variant	Intron 4 of 9	1	NM_000103.4	ENSP00000379683.1

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15635 AN: 152066 Hom.: 972 Cov.: 32

Gnomad AFR AF: 0.0533

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.0807

Gnomad EAS AF: 0.0125

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.106

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

GnomAD4 genome AF: 0.103 AC: 15644 AN: 152184 Hom.: 974 Cov.: 32 AF XY: 0.106 AC XY: 7888 AN XY: 74388

African (AFR) AF: 0.0534 AC: 2218 AN: 41520

American (AMR) AF: 0.186 AC: 2840 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0807 AC: 280 AN: 3470

East Asian (EAS) AF: 0.0125 AC: 65 AN: 5188

South Asian (SAS) AF: 0.150 AC: 723 AN: 4816

European-Finnish (FIN) AF: 0.115 AC: 1217 AN: 10592

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.117 AC: 7980 AN: 67994

Other (OTH) AF: 0.105 AC: 221 AN: 2110

Alfa AF: 0.108 Hom.: 1552

Bravo AF: 0.106

Asia WGS AF: 0.0740 AC: 257 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.29
DANN	Benign	0.35
PhyloP100		-1.5
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: rs12439137; hg19: chr15-51516304;