NM_000103.4:c.-38-21812C>G

Variant names:

• chr15-51264762-G-C
• rs4441215
• NM_000103.4:c.-38-21812C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000103.4(CYP19A1):​c.-38-21812C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 151,866 control chromosomes in the GnomAD database, including 30,257 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 0.62 (30257 hom., cov: 30)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.399
• Publications: 10 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.754 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.-38-21812C>G		intron	N/A	NP_000094.2
	CYP19A1	NM_001347248.1		c.-38-21812C>G		intron	N/A	NP_001334177.1
	CYP19A1	NM_001347249.2		c.-38-21812C>G		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.-38-21812C>G		intron	N/A	ENSP00000379683.1
	CYP19A1	ENST00000439712.6	TSL:1	n.-282-9001C>G		intron	N/A	ENSP00000390614.2
	CYP19A1	ENST00000557934.5	TSL:1	n.-38-21812C>G		intron	N/A	ENSP00000454004.1

Frequencies

GnomAD3 genomes AF: 0.623 AC: 94503 AN: 151748 Hom.: 30222 Cov.: 30

Gnomad AFR AF: 0.761

Gnomad AMI AF: 0.654

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.619

Gnomad SAS AF: 0.582

Gnomad FIN AF: 0.579

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.581

Gnomad OTH AF: 0.592

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

GnomAD4 genome AF: 0.623 AC: 94598 AN: 151866 Hom.: 30257 Cov.: 30 AF XY: 0.619 AC XY: 45896 AN XY: 74202

African (AFR) AF: 0.761 AC: 31542 AN: 41436

American (AMR) AF: 0.487 AC: 7430 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.614 AC: 2127 AN: 3466

East Asian (EAS) AF: 0.619 AC: 3181 AN: 5140

South Asian (SAS) AF: 0.583 AC: 2800 AN: 4800

European-Finnish (FIN) AF: 0.579 AC: 6092 AN: 10520

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.581 AC: 39442 AN: 67928

Other (OTH) AF: 0.592 AC: 1247 AN: 2108

Alfa AF: 0.494 Hom.: 1381

Bravo AF: 0.618

Asia WGS AF: 0.605 AC: 2102 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.42
DANN	Benign	0.52
PhyloP100		-0.40
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4441215; hg19: chr15-51556959;