rs17703883

Variant names:

• chr15-51237900-T-C
• rs17703883
• NM_000103.4:c.146-891A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000103.4(CYP19A1):​c.146-891A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 152,234 control chromosomes in the GnomAD database, including 3,783 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 0.20 (3783 hom., cov: 33)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.970
• Publications: 16 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP19A1	NM_000103.4	c.146-891A>G		intron_variant	Intron 2 of 9	ENST00000396402.6	NP_000094.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP19A1	ENST00000396402.6	c.146-891A>G		intron_variant	Intron 2 of 9	1	NM_000103.4	ENSP00000379683.1

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30773 AN: 152116 Hom.: 3776 Cov.: 33

Gnomad AFR AF: 0.0520

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.202 AC: 30790 AN: 152234 Hom.: 3783 Cov.: 33 AF XY: 0.205 AC XY: 15232 AN XY: 74418

African (AFR) AF: 0.0519 AC: 2156 AN: 41568

American (AMR) AF: 0.297 AC: 4542 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.262 AC: 909 AN: 3472

East Asian (EAS) AF: 0.306 AC: 1585 AN: 5178

South Asian (SAS) AF: 0.205 AC: 992 AN: 4830

European-Finnish (FIN) AF: 0.255 AC: 2701 AN: 10574

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.251 AC: 17057 AN: 68000

Other (OTH) AF: 0.251 AC: 531 AN: 2116

Alfa AF: 0.246 Hom.: 8324

Bravo AF: 0.202

Asia WGS AF: 0.273 AC: 948 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.0
DANN	Benign	0.50
PhyloP100		0.97
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: rs17703883; hg19: chr15-51530097;