rs1902582

Variant names:

• chr15-51288583-A-G
• rs1902582
• NM_000103.4:c.-38-45633T>C

Your query was ambiguous. Multiple possible variants found:

• chr15-51288583-A-G
• chr15-51288583-A-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.-38-45633T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,136 control chromosomes in the GnomAD database, including 3,729 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 (3729 hom., cov: 32)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.160
• Publications: 2 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.388 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.-38-45633T>C		intron	N/A	NP_000094.2
	CYP19A1	NM_001347248.1		c.-39+35233T>C		intron	N/A	NP_001334177.1
	CYP19A1	NM_001347249.2		c.-39+29850T>C		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.-38-45633T>C		intron	N/A	ENSP00000379683.1
	CYP19A1	ENST00000439712.6	TSL:1	n.-282-32822T>C		intron	N/A	ENSP00000390614.2
	CYP19A1	ENST00000557934.5	TSL:1	n.-38-45633T>C		intron	N/A	ENSP00000454004.1

Frequencies

GnomAD3 genomes AF: 0.158 AC: 23989 AN: 152018 Hom.: 3711 Cov.: 32

Gnomad AFR AF: 0.393

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.0547

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.0787

Gnomad MID AF: 0.0541

Gnomad NFE AF: 0.0414

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.158 AC: 24061 AN: 152136 Hom.: 3729 Cov.: 32 AF XY: 0.160 AC XY: 11883 AN XY: 74394

African (AFR) AF: 0.393 AC: 16285 AN: 41446

American (AMR) AF: 0.115 AC: 1762 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0547 AC: 190 AN: 3472

East Asian (EAS) AF: 0.172 AC: 889 AN: 5166

South Asian (SAS) AF: 0.209 AC: 1005 AN: 4812

European-Finnish (FIN) AF: 0.0787 AC: 835 AN: 10612

Middle Eastern (MID) AF: 0.0548 AC: 16 AN: 292

European-Non Finnish (NFE) AF: 0.0414 AC: 2815 AN: 68022

Other (OTH) AF: 0.123 AC: 260 AN: 2112

Alfa AF: 0.109 Hom.: 282

Bravo AF: 0.170

Asia WGS AF: 0.238 AC: 827 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.0
DANN	Benign	0.55
PhyloP100		0.16
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: rs1902582; hg19: chr15-51580780;