rs3751592

Variant names:

• chr15-51314381-T-C
• rs3751592
• NM_000103.4:c.-39+24114A>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.-39+24114A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 151,680 control chromosomes in the GnomAD database, including 7,208 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 0.31 (7208 hom., cov: 31)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06
• Publications: 23 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP19A1	NM_000103.4	c.-39+24114A>G		intron_variant	Intron 1 of 9	ENST00000396402.6	NP_000094.2
CYP19A1	NM_001347248.1	c.-39+9435A>G		intron_variant	Intron 1 of 9		NP_001334177.1
CYP19A1	NM_001347249.2	c.-39+4052A>G		intron_variant	Intron 1 of 9		NP_001334178.1
CYP19A1	NM_031226.3	c.-39+9435A>G		intron_variant	Intron 2 of 10		NP_112503.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP19A1	ENST00000396402.6	c.-39+24114A>G		intron_variant	Intron 1 of 9	1	NM_000103.4	ENSP00000379683.1

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46283 AN: 151562 Hom.: 7205 Cov.: 31

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.322

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

GnomAD4 genome AF: 0.305 AC: 46305 AN: 151680 Hom.: 7208 Cov.: 31 AF XY: 0.303 AC XY: 22438 AN XY: 74132

African (AFR) AF: 0.317 AC: 13092 AN: 41352

American (AMR) AF: 0.349 AC: 5326 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 1025 AN: 3468

East Asian (EAS) AF: 0.112 AC: 570 AN: 5098

South Asian (SAS) AF: 0.260 AC: 1247 AN: 4790

European-Finnish (FIN) AF: 0.261 AC: 2745 AN: 10536

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.316 AC: 21440 AN: 67866

Other (OTH) AF: 0.318 AC: 672 AN: 2110

Alfa AF: 0.319 Hom.: 14857

Bravo AF: 0.316

Asia WGS AF: 0.167 AC: 581 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.42
DANN	Benign	0.52
PhyloP100		-1.1
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: rs3751592; hg19: chr15-51606578;