chr15-51238298-G-A

Variant names:

• chr15-51238298-G-A
• rs16964211
• NM_000103.4:c.146-1289C>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.146-1289C>T 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 152,176 control chromosomes in the GnomAD database, including 2,533 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 (2533 hom., cov: 32)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0690
• Publications: 38 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=-0.74).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000103.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP19A1	NM_000103.4	MANE Select	c.146-1289C>T		intron	N/A	NP_000094.2
	CYP19A1	NM_001347248.1		c.146-1289C>T		intron	N/A	NP_001334177.1
	CYP19A1	NM_001347249.2		c.146-1289C>T		intron	N/A	NP_001334178.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP19A1	ENST00000396402.6	TSL:1 MANE Select	c.146-1289C>T		intron	N/A	ENSP00000379683.1
	CYP19A1	ENST00000559878.5	TSL:1	c.146-1289C>T		intron	N/A	ENSP00000453149.1
	CYP19A1	ENST00000405913.7	TSL:1	c.146-1289C>T		intron	N/A	ENSP00000383930.3

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21252 AN: 152058 Hom.: 2526 Cov.: 32

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0820

Gnomad ASJ AF: 0.0790

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.0786

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0498

Gnomad OTH AF: 0.0946

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

GnomAD4 genome AF: 0.140 AC: 21296 AN: 152176 Hom.: 2533 Cov.: 32 AF XY: 0.144 AC XY: 10682 AN XY: 74390

African (AFR) AF: 0.306 AC: 12682 AN: 41486

American (AMR) AF: 0.0817 AC: 1250 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0790 AC: 274 AN: 3470

East Asian (EAS) AF: 0.253 AC: 1306 AN: 5172

South Asian (SAS) AF: 0.267 AC: 1287 AN: 4826

European-Finnish (FIN) AF: 0.0786 AC: 832 AN: 10590

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

European-Non Finnish (NFE) AF: 0.0498 AC: 3384 AN: 68010

Other (OTH) AF: 0.102 AC: 216 AN: 2116

Alfa AF: 0.0872 Hom.: 2632

Bravo AF: 0.144

Asia WGS AF: 0.302 AC: 1049 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	13
DANN	Benign	0.69
PhyloP100		-0.069
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: rs16964211; hg19: chr15-51530495;