15-51321614-T-C

Variant names:

• chr15-51321614-T-C
• rs1004982
• NM_000103.4:c.-39+16881A>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+16881A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 152,120 control chromosomes in the GnomAD database, including 12,917 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 (12917 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.607
• Publications: 17 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 = 0.48 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP19A1	NM_000103.4	MANE Select	c.-39+16881A>G		intron	N/A	NP_000094.2
	CYP19A1	NM_001347248.1		c.-39+2202A>G		intron	N/A	NP_001334177.1
	CYP19A1	NM_031226.3		c.-39+2202A>G		intron	N/A	NP_112503.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP19A1	ENST00000396402.6	TSL:1 MANE Select	c.-39+16881A>G		intron	N/A	ENSP00000379683.1
	CYP19A1	ENST00000439712.6	TSL:1	n.-283+16881A>G		intron	N/A	ENSP00000390614.2
	CYP19A1	ENST00000557934.5	TSL:1	n.-39+16881A>G		intron	N/A	ENSP00000454004.1

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61416 AN: 152000 Hom.: 12880 Cov.: 32

Gnomad AFR AF: 0.485

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.349

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.416

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.404 AC: 61503 AN: 152120 Hom.: 12917 Cov.: 32 AF XY: 0.400 AC XY: 29774 AN XY: 74356

African (AFR) AF: 0.485 AC: 20123 AN: 41470

American (AMR) AF: 0.464 AC: 7089 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.403 AC: 1397 AN: 3470

East Asian (EAS) AF: 0.299 AC: 1544 AN: 5168

South Asian (SAS) AF: 0.469 AC: 2260 AN: 4822

European-Finnish (FIN) AF: 0.221 AC: 2347 AN: 10598

Middle Eastern (MID) AF: 0.339 AC: 99 AN: 292

European-Non Finnish (NFE) AF: 0.375 AC: 25508 AN: 67986

Other (OTH) AF: 0.417 AC: 880 AN: 2108

Alfa AF: 0.294 Hom.: 992

Bravo AF: 0.428

Asia WGS AF: 0.428 AC: 1488 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	4.9
DANN	Benign	0.68
PhyloP100		0.61
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: rs1004982; hg19: chr15-51613811;