15-51259149-C-G

Variant names:

• chr15-51259149-C-G
• rs10519299
• NM_000103.4:c.-38-16199G>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.-38-16199G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 151,970 control chromosomes in the GnomAD database, including 11,928 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 0.39 (11928 hom., cov: 32)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.233
• Publications: 10 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP19A1	NM_000103.4	c.-38-16199G>C		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.-38-16199G>C		intron_variant	Intron 1 of 9	1	NM_000103.4	ENSP00000379683.1

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58733 AN: 151852 Hom.: 11931 Cov.: 32

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.484

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.500

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.404

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

GnomAD4 genome AF: 0.387 AC: 58747 AN: 151970 Hom.: 11928 Cov.: 32 AF XY: 0.383 AC XY: 28478 AN XY: 74284

African (AFR) AF: 0.279 AC: 11549 AN: 41450

American (AMR) AF: 0.336 AC: 5139 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.496 AC: 1723 AN: 3472

East Asian (EAS) AF: 0.499 AC: 2578 AN: 5164

South Asian (SAS) AF: 0.349 AC: 1682 AN: 4814

European-Finnish (FIN) AF: 0.430 AC: 4525 AN: 10524

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.444 AC: 30157 AN: 67956

Other (OTH) AF: 0.401 AC: 844 AN: 2106

Alfa AF: 0.426 Hom.: 1988

Bravo AF: 0.376

Asia WGS AF: 0.369 AC: 1281 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.0
DANN	Benign	0.56
PhyloP100		0.23
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: rs10519299; hg19: chr15-51551346;