15-51321332-G-A

Variant names:

• chr15-51321332-G-A
• rs1004984
• NM_000103.4:c.-39+17163C>T

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+17163C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 151,742 control chromosomes in the GnomAD database, including 12,486 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 0.40 (12486 hom., cov: 31)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.00
• Publications: 18 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)

LOC112268146 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000103.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP19A1	NM_000103.4	MANE Select	c.-39+17163C>T		intron	N/A	NP_000094.2
	CYP19A1	NM_001347248.1		c.-39+2484C>T		intron	N/A	NP_001334177.1	P11511-1
	CYP19A1	NM_031226.3		c.-39+2484C>T		intron	N/A	NP_112503.1	P11511-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP19A1	ENST00000396402.6	TSL:1 MANE Select	c.-39+17163C>T		intron	N/A	ENSP00000379683.1	P11511-1
	CYP19A1	ENST00000439712.6	TSL:1	n.-283+17163C>T		intron	N/A	ENSP00000390614.2	E7EQ08
	CYP19A1	ENST00000557934.5	TSL:1	n.-39+17163C>T		intron	N/A	ENSP00000454004.1	E7EQ08

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60370 AN: 151624 Hom.: 12450 Cov.: 31

Gnomad AFR AF: 0.469

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.373

Gnomad OTH AF: 0.410

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

GnomAD4 genome AF: 0.398 AC: 60455 AN: 151742 Hom.: 12486 Cov.: 31 AF XY: 0.395 AC XY: 29283 AN XY: 74132

African (AFR) AF: 0.469 AC: 19396 AN: 41338

American (AMR) AF: 0.459 AC: 7005 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.403 AC: 1397 AN: 3468

East Asian (EAS) AF: 0.299 AC: 1541 AN: 5146

South Asian (SAS) AF: 0.466 AC: 2241 AN: 4804

European-Finnish (FIN) AF: 0.221 AC: 2328 AN: 10524

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.373 AC: 25329 AN: 67900

Other (OTH) AF: 0.412 AC: 865 AN: 2102

Alfa AF: 0.387 Hom.: 18358

Bravo AF: 0.421

Asia WGS AF: 0.424 AC: 1475 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.41
DANN	Benign	0.17
PhyloP100		-3.0
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: rs1004984; hg19: chr15-51613529;