chr15-51221725-G-C

Variant names:

• chr15-51221725-G-C
• rs6493488
• ENST00000405913.7:c.*595C>G

Variant summary

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

The ENST00000405913.7(CYP19A1):​c.*595C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 152,640 control chromosomes in the GnomAD database, including 14,929 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 0.43 (14843 hom., cov: 33)
  • Exomes 𝑓: 0.49 (86 hom.)
• Consequence: CYP19A1 ENST00000405913.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.331
• Publications: 7 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000405913.7. 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.628+624C>G		intron	N/A	NP_000094.2
	CYP19A1	NM_001347248.1		c.628+624C>G		intron	N/A	NP_001334177.1
	CYP19A1	NM_001347249.2		c.628+624C>G		intron	N/A	NP_001334178.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP19A1	ENST00000405913.7	TSL:1	c.*595C>G		3_prime_UTR	Exon 4 of 4	ENSP00000383930.3
	CYP19A1	ENST00000396402.6	TSL:1 MANE Select	c.628+624C>G		intron	N/A	ENSP00000379683.1
	CYP19A1	ENST00000559878.5	TSL:1	c.628+624C>G		intron	N/A	ENSP00000453149.1

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64705 AN: 151916 Hom.: 14845 Cov.: 33

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.493

Gnomad MID AF: 0.436

Gnomad NFE AF: 0.526

Gnomad OTH AF: 0.449

GnomAD4 exome AF: 0.490 AC: 297 AN: 606 Hom.: 86 Cov.: 0 AF XY: 0.478 AC XY: 152 AN XY: 318

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.352 AC: 38 AN: 108

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

East Asian (EAS) AF: 0.300 AC: 3 AN: 10

South Asian (SAS) AF: 0.318 AC: 7 AN: 22

European-Finnish (FIN) AF: 0.500 AC: 2 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.537 AC: 233 AN: 434

Other (OTH) AF: 0.500 AC: 13 AN: 26

GnomAD4 genome AF: 0.426 AC: 64721 AN: 152034 Hom.: 14843 Cov.: 33 AF XY: 0.422 AC XY: 31400 AN XY: 74342

African (AFR) AF: 0.245 AC: 10144 AN: 41464

American (AMR) AF: 0.371 AC: 5676 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 1923 AN: 3468

East Asian (EAS) AF: 0.497 AC: 2574 AN: 5176

South Asian (SAS) AF: 0.392 AC: 1890 AN: 4822

European-Finnish (FIN) AF: 0.493 AC: 5201 AN: 10550

Middle Eastern (MID) AF: 0.438 AC: 128 AN: 292

European-Non Finnish (NFE) AF: 0.526 AC: 35765 AN: 67958

Other (OTH) AF: 0.447 AC: 943 AN: 2108

Alfa AF: 0.479 Hom.: 2219

Bravo AF: 0.411

Asia WGS AF: 0.384 AC: 1334 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.1
DANN	Benign	0.36
PhyloP100		0.33
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: rs6493488; hg19: chr15-51513922;