15-51227748-AAAG-AAAGAAG

Position:

• chr15-51227748-AAAG-AAAGAAG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000103.4(CYP19A1):​c.451+28_451+30dupCTT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.66 (32641 hom., cov: 0)
  • Exomes 𝑓: 0.62 (163251 hom.)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.579

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:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 15-51227748-A-AAAG is Benign according to our data. Variant chr15-51227748-A-AAAG is described in ClinVar as [Benign]. Clinvar id is 1247292.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP19A1	NM_000103.4	c.451+28_451+30dupCTT		intron_variant		ENST00000396402.6	NP_000094.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP19A1	ENST00000396402.6	c.451+28_451+30dupCTT		intron_variant		1	NM_000103.4	ENSP00000379683.1

Frequencies

GnomAD3 genomes AF: 0.657 AC: 99221 AN: 151014 Hom.: 32600 Cov.: 0

Gnomad AFR AF: 0.675

Gnomad AMI AF: 0.631

Gnomad AMR AF: 0.612

Gnomad ASJ AF: 0.678

Gnomad EAS AF: 0.688

Gnomad SAS AF: 0.746

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.649

Gnomad OTH AF: 0.622

GnomAD3 exomes AF: 0.658 AC: 157528 AN: 239336 Hom.: 52875 AF XY: 0.662 AC XY: 85741 AN XY: 129532

Gnomad AFR exome AF: 0.673

Gnomad AMR exome AF: 0.599

Gnomad ASJ exome AF: 0.666

Gnomad EAS exome AF: 0.686

Gnomad SAS exome AF: 0.748

Gnomad FIN exome AF: 0.660

Gnomad NFE exome AF: 0.646

Gnomad OTH exome AF: 0.636

GnomAD4 exome AF: 0.620 AC: 489656 AN: 789848 Hom.: 163251 Cov.: 12 AF XY: 0.626 AC XY: 261950 AN XY: 418202

Gnomad4 AFR exome AF: 0.643

Gnomad4 AMR exome AF: 0.584

Gnomad4 ASJ exome AF: 0.653

Gnomad4 EAS exome AF: 0.696

Gnomad4 SAS exome AF: 0.715

Gnomad4 FIN exome AF: 0.649

Gnomad4 NFE exome AF: 0.601

Gnomad4 OTH exome AF: 0.616

GnomAD4 genome AF: 0.657 AC: 99315 AN: 151132 Hom.: 32641 Cov.: 0 AF XY: 0.659 AC XY: 48669 AN XY: 73834

Gnomad4 AFR AF: 0.676

Gnomad4 AMR AF: 0.611

Gnomad4 ASJ AF: 0.678

Gnomad4 EAS AF: 0.687

Gnomad4 SAS AF: 0.746

Gnomad4 FIN AF: 0.657

Gnomad4 NFE AF: 0.649

Gnomad4 OTH AF: 0.623

Alfa AF: 0.647 Hom.: 5351

Asia WGS AF: 0.686 AC: 2384 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11575899; hg19: chr15-51519945;