rs17703883

Positions:

• chr15-51237900-T-C

Variant summary

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

The NM_000103.4(CYP19A1):​c.146-891A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 152,234 control chromosomes in the GnomAD database, including 3,783 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 0.20 (3783 hom., cov: 33)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.970

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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP19A1	NM_000103.4	c.146-891A>G		intron_variant		ENST00000396402.6
MIR4713HG	NR_146310.1	n.195-40083T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP19A1	ENST00000396402.6	c.146-891A>G		intron_variant		1	NM_000103.4	P1
MIR4713HG	ENST00000559909.1	n.195-40083T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30773 AN: 152116 Hom.: 3776 Cov.: 33

Gnomad AFR AF: 0.0520

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.202 AC: 30790 AN: 152234 Hom.: 3783 Cov.: 33 AF XY: 0.205 AC XY: 15232 AN XY: 74418

Gnomad4 AFR AF: 0.0519

Gnomad4 AMR AF: 0.297

Gnomad4 ASJ AF: 0.262

Gnomad4 EAS AF: 0.306

Gnomad4 SAS AF: 0.205

Gnomad4 FIN AF: 0.255

Gnomad4 NFE AF: 0.251

Gnomad4 OTH AF: 0.251

Alfa AF: 0.252 Hom.: 6817

Bravo AF: 0.202

Asia WGS AF: 0.273 AC: 948 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.0
DANN	Benign	0.50

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: rs17703883; hg19: chr15-51530097;