rs10519301

Positions:

• chr15-51307340-G-A

Variant summary

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

The NM_000103.4(CYP19A1):​c.-39+31155C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0361 in 152,292 control chromosomes in the GnomAD database, including 264 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 0.036 (264 hom., cov: 32)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17

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]

LOC124903493 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP19A1	NM_000103.4	c.-39+31155C>T		intron_variant		ENST00000396402.6
LOC124903493	XR_007064634.1	n.12245G>A		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP19A1	ENST00000396402.6	c.-39+31155C>T		intron_variant		1	NM_000103.4	P1

Frequencies

GnomAD3 genomes AF: 0.0360 AC: 5477 AN: 152174 Hom.: 264 Cov.: 32

Gnomad AFR AF: 0.0904

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0154

Gnomad ASJ AF: 0.0135

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.0487

Gnomad FIN AF: 0.00207

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.00551

Gnomad OTH AF: 0.0277

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

GnomAD4 genome AF: 0.0361 AC: 5496 AN: 152292 Hom.: 264 Cov.: 32 AF XY: 0.0354 AC XY: 2635 AN XY: 74472

Gnomad4 AFR AF: 0.0908

Gnomad4 AMR AF: 0.0154

Gnomad4 ASJ AF: 0.0135

Gnomad4 EAS AF: 0.143

Gnomad4 SAS AF: 0.0481

Gnomad4 FIN AF: 0.00207

Gnomad4 NFE AF: 0.00551

Gnomad4 OTH AF: 0.0279

Alfa AF: 0.0122 Hom.: 94

Bravo AF: 0.0396

Asia WGS AF: 0.0840 AC: 292 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.021
DANN	Benign	0.46

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

Publications

LitVar

Other links and lift over

dbSNP: rs10519301; hg19: chr15-51599537;