rs3784308

chr15-51235201-A-G

Variant summary

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

The NM_000103.4(CYP19A1):c.296+1658T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,236 control chromosomes in the GnomAD database, including 2,045 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 0.13 (2045 hom., cov: 32)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0570

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP19A1	NM_000103.4	c.296+1658T>C		intron_variant		ENST00000396402.6
MIR4713HG	NR_146310.1	n.195-42782A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP19A1	ENST00000396402.6	c.296+1658T>C		intron_variant		1	NM_000103.4	P1
MIR4713HG	ENST00000559909.1	n.195-42782A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19166 AN: 152118 Hom.: 2041 Cov.: 32

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0795

Gnomad ASJ AF: 0.0755

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.0646

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0450

Gnomad OTH AF: 0.0894

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

GnomAD4 genome AF: 0.126 AC: 19202 AN: 152236 Hom.: 2045 Cov.: 32 AF XY: 0.130 AC XY: 9684 AN XY: 74426

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.0792

Gnomad4 ASJ AF: 0.0755

Gnomad4 EAS AF: 0.254

Gnomad4 SAS AF: 0.267

Gnomad4 FIN AF: 0.0646

Gnomad4 NFE AF: 0.0450

Gnomad4 OTH AF: 0.0970

Alfa AF: 0.0771 Hom.: 410

Bravo AF: 0.131

Asia WGS AF: 0.298 AC: 1035 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	1.8
Dann	Benign	0.25

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: rs3784308; hg19: chr15-51527398;