rs2470152

Variant names:

• chr15-51302775-G-A
• rs2470152
• NM_000103.4:c.-39+35720C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-51302775-G-A
• chr15-51302775-G-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+35720C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.499 in 152,116 control chromosomes in the GnomAD database, including 19,131 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 0.50 (19131 hom., cov: 33)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0660
• Publications: 44 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP19A1	NM_000103.4	c.-39+35720C>T		intron_variant	Intron 1 of 9	ENST00000396402.6	NP_000094.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP19A1	ENST00000396402.6	c.-39+35720C>T		intron_variant	Intron 1 of 9	1	NM_000103.4	ENSP00000379683.1

Frequencies

GnomAD3 genomes AF: 0.499 AC: 75838 AN: 151998 Hom.: 19125 Cov.: 33

Gnomad AFR AF: 0.530

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.516

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

GnomAD4 genome AF: 0.499 AC: 75887 AN: 152116 Hom.: 19131 Cov.: 33 AF XY: 0.497 AC XY: 36979 AN XY: 74368

African (AFR) AF: 0.530 AC: 21999 AN: 41506

American (AMR) AF: 0.559 AC: 8543 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.444 AC: 1541 AN: 3472

East Asian (EAS) AF: 0.490 AC: 2536 AN: 5176

South Asian (SAS) AF: 0.466 AC: 2249 AN: 4822

European-Finnish (FIN) AF: 0.440 AC: 4642 AN: 10562

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.482 AC: 32784 AN: 67970

Other (OTH) AF: 0.514 AC: 1085 AN: 2112

Alfa AF: 0.492 Hom.: 36595

Bravo AF: 0.510

Asia WGS AF: 0.489 AC: 1703 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.9
DANN	Benign	0.76
PhyloP100		0.066
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: rs2470152; hg19: chr15-51594972;