rs726547

Positions:

• chr15-51237970-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.146-961C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,086 control chromosomes in the GnomAD database, including 3,378 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 0.16 (3378 hom., cov: 33)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP19A1	NM_000103.4	c.146-961C>T		intron_variant		ENST00000396402.6
MIR4713HG	NR_146310.1	n.195-40013G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP19A1	ENST00000396402.6	c.146-961C>T		intron_variant		1	NM_000103.4	P1
MIR4713HG	ENST00000559909.1	n.195-40013G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23735 AN: 151966 Hom.: 3362 Cov.: 33

Gnomad AFR AF: 0.363

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0863

Gnomad ASJ AF: 0.0798

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.0785

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0499

Gnomad OTH AF: 0.103

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

GnomAD4 genome AF: 0.156 AC: 23796 AN: 152086 Hom.: 3378 Cov.: 33 AF XY: 0.159 AC XY: 11802 AN XY: 74336

Gnomad4 AFR AF: 0.364

Gnomad4 AMR AF: 0.0860

Gnomad4 ASJ AF: 0.0798

Gnomad4 EAS AF: 0.253

Gnomad4 SAS AF: 0.268

Gnomad4 FIN AF: 0.0785

Gnomad4 NFE AF: 0.0499

Gnomad4 OTH AF: 0.110

Alfa AF: 0.111 Hom.: 313

Bravo AF: 0.162

Asia WGS AF: 0.310 AC: 1078 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.12
DANN	Benign	0.66

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: rs726547; hg19: chr15-51530167;