rs749292

chr15-51266534-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.-38-23584C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 152,100 control chromosomes in the GnomAD database, including 14,952 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 0.44 (14952 hom., cov: 33)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.574

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP19A1	NM_000103.4	c.-38-23584C>T		intron_variant		ENST00000396402.6
MIR4713HG	NR_146310.1	n.195-11449G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP19A1	ENST00000396402.6	c.-38-23584C>T		intron_variant		1	NM_000103.4	P1
MIR4713HG	ENST00000559909.1	n.195-11449G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.441 AC: 67030 AN: 151982 Hom.: 14951 Cov.: 33

Gnomad AFR AF: 0.478

Gnomad AMI AF: 0.484

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.446

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.440

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

GnomAD4 genome AF: 0.441 AC: 67062 AN: 152100 Hom.: 14952 Cov.: 33 AF XY: 0.435 AC XY: 32352 AN XY: 74350

Gnomad4 AFR AF: 0.477

Gnomad4 AMR AF: 0.362

Gnomad4 ASJ AF: 0.496

Gnomad4 EAS AF: 0.446

Gnomad4 SAS AF: 0.344

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.442

Gnomad4 OTH AF: 0.436

Alfa AF: 0.437 Hom.: 29746

Bravo AF: 0.438

Asia WGS AF: 0.368 AC: 1280 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	7.6
Dann	Benign	0.65

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: rs749292; hg19: chr15-51558731;