15-51321709-C-G

Variant names:

• chr15-51321709-C-G
• rs1902585
• NM_000103.4:c.-39+16786G>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.-39+16786G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.565 in 152,148 control chromosomes in the GnomAD database, including 26,944 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 0.56 (26939 hom., cov: 32)
  • Exomes 𝑓: 0.38 (5 hom.)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.429
• 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)

LOC112268146 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.836 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+16786G>C		intron	N/A	NP_000094.2
	CYP19A1	NM_001347248.1		c.-39+2107G>C		intron	N/A	NP_001334177.1	P11511-1
	CYP19A1	NM_031226.3		c.-39+2107G>C		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+16786G>C		intron	N/A	ENSP00000379683.1	P11511-1
	CYP19A1	ENST00000439712.6	TSL:1	n.-283+16786G>C		intron	N/A	ENSP00000390614.2	E7EQ08
	CYP19A1	ENST00000557934.5	TSL:1	n.-39+16786G>C		intron	N/A	ENSP00000454004.1	E7EQ08

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85753 AN: 151938 Hom.: 26866 Cov.: 32

Gnomad AFR AF: 0.843

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.588

Gnomad ASJ AF: 0.434

Gnomad EAS AF: 0.584

Gnomad SAS AF: 0.508

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.553

GnomAD4 exome AF: 0.380 AC: 35 AN: 92 Hom.: 5 Cov.: 0 AF XY: 0.394 AC XY: 26 AN XY: 66

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.354 AC: 29 AN: 82

Other (OTH) AF: 0.500 AC: 2 AN: 4

GnomAD4 genome AF: 0.565 AC: 85886 AN: 152056 Hom.: 26939 Cov.: 32 AF XY: 0.559 AC XY: 41509 AN XY: 74320

African (AFR) AF: 0.843 AC: 34979 AN: 41498

American (AMR) AF: 0.589 AC: 9005 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.434 AC: 1504 AN: 3464

East Asian (EAS) AF: 0.585 AC: 3008 AN: 5146

South Asian (SAS) AF: 0.507 AC: 2441 AN: 4810

European-Finnish (FIN) AF: 0.306 AC: 3232 AN: 10566

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.443 AC: 30091 AN: 67972

Other (OTH) AF: 0.556 AC: 1176 AN: 2116

Alfa AF: 0.482 Hom.: 2307

Bravo AF: 0.604

Asia WGS AF: 0.586 AC: 2036 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.6
DANN	Benign	0.77
PhyloP100		-0.43
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: rs1902585; hg19: chr15-51613906;