15-51227748-AAAG-AAAGAAG

Variant names:

• chr15-51227748-A-AAAG
• rs11575899
• NM_000103.4:c.451+28_451+30dupCTT

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 24 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000103.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP19A1	NM_000103.4	MANE Select	c.451+28_451+30dupCTT		intron	N/A	NP_000094.2
	CYP19A1	NM_001347248.1		c.451+28_451+30dupCTT		intron	N/A	NP_001334177.1
	CYP19A1	NM_001347249.2		c.451+28_451+30dupCTT		intron	N/A	NP_001334178.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP19A1	ENST00000396402.6	TSL:1 MANE Select	c.451+30_451+31insCTT		intron	N/A	ENSP00000379683.1
	CYP19A1	ENST00000559878.5	TSL:1	c.451+30_451+31insCTT		intron	N/A	ENSP00000453149.1
	CYP19A1	ENST00000405913.7	TSL:1	c.451+30_451+31insCTT		intron	N/A	ENSP00000383930.3

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

GnomAD2 exomes AF: 0.658 AC: 157528 AN: 239336 AF XY: 0.662

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 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

African (AFR) AF: 0.643 AC: 13060 AN: 20310

American (AMR) AF: 0.584 AC: 24705 AN: 42300

Ashkenazi Jewish (ASJ) AF: 0.653 AC: 13976 AN: 21398

East Asian (EAS) AF: 0.696 AC: 25214 AN: 36246

South Asian (SAS) AF: 0.715 AC: 48145 AN: 67318

European-Finnish (FIN) AF: 0.649 AC: 33435 AN: 51546

Middle Eastern (MID) AF: 0.541 AC: 2405 AN: 4442

European-Non Finnish (NFE) AF: 0.601 AC: 305414 AN: 508442

Other (OTH) AF: 0.616 AC: 23302 AN: 37846

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

African (AFR) AF: 0.676 AC: 27660 AN: 40944

American (AMR) AF: 0.611 AC: 9307 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.678 AC: 2351 AN: 3470

East Asian (EAS) AF: 0.687 AC: 3515 AN: 5118

South Asian (SAS) AF: 0.746 AC: 3582 AN: 4800

European-Finnish (FIN) AF: 0.657 AC: 6832 AN: 10400

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.649 AC: 44023 AN: 67864

Other (OTH) AF: 0.623 AC: 1309 AN: 2102

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

Jun 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.58
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs11575899; hg19: chr15-51519945;