rs2445759

Positions:

• chr15-51308644-G-T

Variant summary

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

The NM_000103.4(CYP19A1):​c.-39+29851C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0702 in 152,094 control chromosomes in the GnomAD database, including 420 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 0.070 (420 hom., cov: 32)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.122

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0801 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP19A1	NM_000103.4	c.-39+29851C>A		intron_variant		ENST00000396402.6
LOC124903493	XR_007064634.1	n.13160-318G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP19A1	ENST00000396402.6	c.-39+29851C>A		intron_variant		1	NM_000103.4	P1

Frequencies

GnomAD3 genomes AF: 0.0703 AC: 10680 AN: 151976 Hom.: 421 Cov.: 32

Gnomad AFR AF: 0.0827

Gnomad AMI AF: 0.0714

Gnomad AMR AF: 0.0570

Gnomad ASJ AF: 0.0464

Gnomad EAS AF: 0.00560

Gnomad SAS AF: 0.0337

Gnomad FIN AF: 0.0516

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0770

Gnomad OTH AF: 0.0808

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

GnomAD4 genome AF: 0.0702 AC: 10674 AN: 152094 Hom.: 420 Cov.: 32 AF XY: 0.0669 AC XY: 4973 AN XY: 74328

Gnomad4 AFR AF: 0.0824

Gnomad4 AMR AF: 0.0569

Gnomad4 ASJ AF: 0.0464

Gnomad4 EAS AF: 0.00561

Gnomad4 SAS AF: 0.0342

Gnomad4 FIN AF: 0.0516

Gnomad4 NFE AF: 0.0770

Gnomad4 OTH AF: 0.0790

Alfa AF: 0.0730 Hom.: 86

Bravo AF: 0.0712

Asia WGS AF: 0.0260 AC: 89 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.98
DANN	Benign	0.69

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: rs2445759; hg19: chr15-51600841;