rs12594287

chr15-51231710-G-Achr15-51231710-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.297-3777C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 151,656 control chromosomes in the GnomAD database, including 2,519 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 0.14 (2519 hom., cov: 30)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.299

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP19A1	NM_000103.4	c.297-3777C>T		intron_variant		ENST00000396402.6
MIR4713HG	NR_146310.1	n.195-46273G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP19A1	ENST00000396402.6	c.297-3777C>T		intron_variant		1	NM_000103.4	P1
MIR4713HG	ENST00000559909.1	n.195-46273G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21136 AN: 151536 Hom.: 2512 Cov.: 30

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0817

Gnomad ASJ AF: 0.0802

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.0780

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0499

Gnomad OTH AF: 0.0940

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

GnomAD4 genome AF: 0.140 AC: 21180 AN: 151656 Hom.: 2519 Cov.: 30 AF XY: 0.143 AC XY: 10599 AN XY: 74136

Gnomad4 AFR AF: 0.306

Gnomad4 AMR AF: 0.0814

Gnomad4 ASJ AF: 0.0802

Gnomad4 EAS AF: 0.252

Gnomad4 SAS AF: 0.266

Gnomad4 FIN AF: 0.0780

Gnomad4 NFE AF: 0.0498

Gnomad4 OTH AF: 0.102

Alfa AF: 0.0543 Hom.: 106

Bravo AF: 0.144

Asia WGS AF: 0.303 AC: 1051 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	5.4
Dann	Benign	0.83

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: rs12594287; hg19: chr15-51523907;