15-51297703-A-G

Variant names:

• chr15-51297703-A-G
• rs2470157
• NM_000103.4:c.-39+40792T>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.-39+40792T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0994 in 151,764 control chromosomes in the GnomAD database, including 860 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 0.099 (860 hom., cov: 31)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.53
• 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]

LOC124903493 (HGNC:):

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.129 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.-39+40792T>C		intron	N/A	NP_000094.2
	CYP19A1	NM_001347248.1		c.-39+26113T>C		intron	N/A	NP_001334177.1
	CYP19A1	NM_001347249.2		c.-39+20730T>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.-39+40792T>C		intron	N/A	ENSP00000379683.1
	CYP19A1	ENST00000439712.6	TSL:1	n.-283+40792T>C		intron	N/A	ENSP00000390614.2
	CYP19A1	ENST00000557934.5	TSL:1	n.-39+40792T>C		intron	N/A	ENSP00000454004.1

Frequencies

GnomAD3 genomes AF: 0.0995 AC: 15083 AN: 151646 Hom.: 859 Cov.: 31

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.0760

Gnomad ASJ AF: 0.0609

Gnomad EAS AF: 0.00579

Gnomad SAS AF: 0.0474

Gnomad FIN AF: 0.0649

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.106

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

GnomAD4 genome AF: 0.0994 AC: 15088 AN: 151764 Hom.: 860 Cov.: 31 AF XY: 0.0944 AC XY: 7003 AN XY: 74182

African (AFR) AF: 0.132 AC: 5446 AN: 41326

American (AMR) AF: 0.0759 AC: 1157 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.0609 AC: 211 AN: 3464

East Asian (EAS) AF: 0.00580 AC: 30 AN: 5170

South Asian (SAS) AF: 0.0476 AC: 228 AN: 4786

European-Finnish (FIN) AF: 0.0649 AC: 685 AN: 10548

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.103 AC: 6982 AN: 67930

Other (OTH) AF: 0.104 AC: 218 AN: 2102

Alfa AF: 0.101 Hom.: 332

Bravo AF: 0.102

Asia WGS AF: 0.0330 AC: 114 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.9
DANN	Benign	0.68
PhyloP100		1.5
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: rs2470157; hg19: chr15-51589900;