NM_000103.4:c.146-961C>T

Variant names:

• chr15-51237970-G-A
• rs726547
• NM_000103.4:c.146-961C>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.146-961C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,086 control chromosomes in the GnomAD database, including 3,378 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 0.16 (3378 hom., cov: 33)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 11 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP19A1	NM_000103.4	c.146-961C>T		intron_variant	Intron 2 of 9	ENST00000396402.6	NP_000094.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP19A1	ENST00000396402.6	c.146-961C>T		intron_variant	Intron 2 of 9	1	NM_000103.4	ENSP00000379683.1

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23735 AN: 151966 Hom.: 3362 Cov.: 33

Gnomad AFR AF: 0.363

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0863

Gnomad ASJ AF: 0.0798

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.0785

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0499

Gnomad OTH AF: 0.103

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

GnomAD4 genome AF: 0.156 AC: 23796 AN: 152086 Hom.: 3378 Cov.: 33 AF XY: 0.159 AC XY: 11802 AN XY: 74336

African (AFR) AF: 0.364 AC: 15082 AN: 41448

American (AMR) AF: 0.0860 AC: 1315 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0798 AC: 277 AN: 3472

East Asian (EAS) AF: 0.253 AC: 1311 AN: 5180

South Asian (SAS) AF: 0.268 AC: 1289 AN: 4816

European-Finnish (FIN) AF: 0.0785 AC: 830 AN: 10574

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

European-Non Finnish (NFE) AF: 0.0499 AC: 3394 AN: 67990

Other (OTH) AF: 0.110 AC: 233 AN: 2114

Alfa AF: 0.118 Hom.: 355

Bravo AF: 0.162

Asia WGS AF: 0.310 AC: 1078 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.12
DANN	Benign	0.66
PhyloP100		-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: rs726547; hg19: chr15-51530167;