rs6493497

Positions:

• chr15-51338638-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The variant allele was found at a frequency of 0.164 in 152,192 control chromosomes in the GnomAD database, including 2,353 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 0.16 (2353 hom., cov: 32)
  • Exomes 𝑓: 0.038 (0 hom.)
• Consequence: intergenic_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365

Genes affected

(HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.51338638G>A		intergenic_region
CYP19A1	NM_000103.4	c.-182C>T		upstream_gene_variant		ENST00000396402.6	NP_000094.2
CYP19A1	NM_031226.3	c.-291C>T		upstream_gene_variant			NP_112503.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP19A1	ENST00000396402.6	c.-182C>T		upstream_gene_variant		1	NM_000103.4	ENSP00000379683.1

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24934 AN: 152046 Hom.: 2340 Cov.: 32

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.0637

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.166

GnomAD4 exome AF: 0.0385 AC: 1 AN: 26 Hom.: 0 Cov.: 0 AF XY: 0.0556 AC XY: 1 AN XY: 18

Gnomad4 NFE exome AF: 0.0556

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.164 AC: 24996 AN: 152166 Hom.: 2353 Cov.: 32 AF XY: 0.165 AC XY: 12275 AN XY: 74396

Gnomad4 AFR AF: 0.257

Gnomad4 AMR AF: 0.157

Gnomad4 ASJ AF: 0.139

Gnomad4 EAS AF: 0.206

Gnomad4 SAS AF: 0.259

Gnomad4 FIN AF: 0.0637

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.170

Alfa AF: 0.129 Hom.: 1362

Bravo AF: 0.175

Asia WGS AF: 0.284 AC: 987 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.7
DANN	Benign	0.50

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6493497; hg19: chr15-51630835;