15-51261835-C-T

Variant names:

• chr15-51261835-C-T
• rs17523527
• NM_000103.4:c.-38-18885G>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.-38-18885G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 152,008 control chromosomes in the GnomAD database, including 10,441 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 0.34 (10441 hom., cov: 32)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48
• Publications: 6 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP19A1	NM_000103.4	c.-38-18885G>A		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.-38-18885G>A		intron_variant	Intron 1 of 9	1	NM_000103.4	ENSP00000379683.1

Frequencies

GnomAD3 genomes AF: 0.342 AC: 51936 AN: 151892 Hom.: 10444 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.485

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.495

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.344

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.367

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

GnomAD4 genome AF: 0.342 AC: 51940 AN: 152008 Hom.: 10441 Cov.: 32 AF XY: 0.341 AC XY: 25358 AN XY: 74320

African (AFR) AF: 0.126 AC: 5242 AN: 41458

American (AMR) AF: 0.322 AC: 4916 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.495 AC: 1717 AN: 3468

East Asian (EAS) AF: 0.497 AC: 2569 AN: 5164

South Asian (SAS) AF: 0.348 AC: 1675 AN: 4814

European-Finnish (FIN) AF: 0.430 AC: 4548 AN: 10580

Middle Eastern (MID) AF: 0.360 AC: 105 AN: 292

European-Non Finnish (NFE) AF: 0.441 AC: 29956 AN: 67934

Other (OTH) AF: 0.365 AC: 771 AN: 2112

Alfa AF: 0.411 Hom.: 2770

Bravo AF: 0.324

Asia WGS AF: 0.358 AC: 1244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.16
DANN	Benign	0.40
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: rs17523527; hg19: chr15-51554032;