rs2899470

Variant names:

• chr15-51211480-T-G
• rs2899470
• NM_000103.4:c.1264-424A>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.1264-424A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.588 in 152,120 control chromosomes in the GnomAD database, including 26,696 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 0.59 (26696 hom., cov: 33)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.372
• Publications: 18 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP19A1	NM_000103.4	c.1264-424A>C		intron_variant	Intron 9 of 9	ENST00000396402.6	NP_000094.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP19A1	ENST00000396402.6	c.1264-424A>C		intron_variant	Intron 9 of 9	1	NM_000103.4	ENSP00000379683.1

Frequencies

GnomAD3 genomes AF: 0.588 AC: 89311 AN: 152002 Hom.: 26667 Cov.: 33

Gnomad AFR AF: 0.679

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.681

Gnomad SAS AF: 0.595

Gnomad FIN AF: 0.568

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.538

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

GnomAD4 genome AF: 0.588 AC: 89390 AN: 152120 Hom.: 26696 Cov.: 33 AF XY: 0.586 AC XY: 43554 AN XY: 74376

African (AFR) AF: 0.680 AC: 28189 AN: 41482

American (AMR) AF: 0.439 AC: 6705 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.612 AC: 2126 AN: 3472

East Asian (EAS) AF: 0.681 AC: 3532 AN: 5188

South Asian (SAS) AF: 0.597 AC: 2881 AN: 4826

European-Finnish (FIN) AF: 0.568 AC: 6013 AN: 10582

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.561 AC: 38168 AN: 67980

Other (OTH) AF: 0.539 AC: 1137 AN: 2108

Alfa AF: 0.598 Hom.: 4147

Bravo AF: 0.580

Asia WGS AF: 0.612 AC: 2130 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.8
DANN	Benign	0.75
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: rs2899470; hg19: chr15-51503677;