15-51256585-C-T

Variant names:

• chr15-51256585-C-T
• rs2414099
• NM_000103.4:c.-38-13635G>A

Variant summary

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

The NM_000103.4(CYP19A1):​c.-38-13635G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.832 in 152,136 control chromosomes in the GnomAD database, including 52,877 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 0.83 (52877 hom., cov: 32)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.316
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.964 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.-38-13635G>A		intron	N/A	NP_000094.2
	CYP19A1	NM_001347248.1		c.-38-13635G>A		intron	N/A	NP_001334177.1
	CYP19A1	NM_001347249.2		c.-38-13635G>A		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.-38-13635G>A		intron	N/A	ENSP00000379683.1
	CYP19A1	ENST00000439712.6	TSL:1	n.-282-824G>A		intron	N/A	ENSP00000390614.2
	CYP19A1	ENST00000557934.5	TSL:1	n.-38-13635G>A		intron	N/A	ENSP00000454004.1

Frequencies

GnomAD3 genomes AF: 0.832 AC: 126500 AN: 152018 Hom.: 52841 Cov.: 32

Gnomad AFR AF: 0.815

Gnomad AMI AF: 0.883

Gnomad AMR AF: 0.769

Gnomad ASJ AF: 0.882

Gnomad EAS AF: 0.987

Gnomad SAS AF: 0.790

Gnomad FIN AF: 0.852

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.841

Gnomad OTH AF: 0.840

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

GnomAD4 genome AF: 0.832 AC: 126591 AN: 152136 Hom.: 52877 Cov.: 32 AF XY: 0.831 AC XY: 61816 AN XY: 74406

African (AFR) AF: 0.814 AC: 33780 AN: 41476

American (AMR) AF: 0.769 AC: 11745 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.882 AC: 3062 AN: 3470

East Asian (EAS) AF: 0.987 AC: 5117 AN: 5184

South Asian (SAS) AF: 0.791 AC: 3811 AN: 4818

European-Finnish (FIN) AF: 0.852 AC: 9023 AN: 10590

Middle Eastern (MID) AF: 0.864 AC: 254 AN: 294

European-Non Finnish (NFE) AF: 0.841 AC: 57219 AN: 68006

Other (OTH) AF: 0.841 AC: 1775 AN: 2110

Alfa AF: 0.838 Hom.: 171722

Bravo AF: 0.825

Asia WGS AF: 0.892 AC: 3103 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.69
PhyloP100		-0.32
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: rs2414099; hg19: chr15-51548782;