15-51261712-A-G

Variant names:

• chr15-51261712-A-G
• rs17601876
• NM_000103.4:c.-38-18762T>C

Variant summary

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

The NM_000103.4(CYP19A1):​c.-38-18762T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 151,994 control chromosomes in the GnomAD database, including 26,889 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 0.57 (26889 hom., cov: 32)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.452
• Publications: 20 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.799 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP19A1	NM_000103.4	MANE Select	c.-38-18762T>C		intron	N/A	NP_000094.2
	CYP19A1	NM_001347248.1		c.-38-18762T>C		intron	N/A	NP_001334177.1	P11511-1
	CYP19A1	NM_001347249.2		c.-38-18762T>C		intron	N/A	NP_001334178.1	P11511-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP19A1	ENST00000396402.6	TSL:1 MANE Select	c.-38-18762T>C		intron	N/A	ENSP00000379683.1	P11511-1
	CYP19A1	ENST00000439712.6	TSL:1	n.-282-5951T>C		intron	N/A	ENSP00000390614.2	E7EQ08
	CYP19A1	ENST00000557934.5	TSL:1	n.-38-18762T>C		intron	N/A	ENSP00000454004.1	E7EQ08

Frequencies

GnomAD3 genomes AF: 0.573 AC: 87077 AN: 151876 Hom.: 26846 Cov.: 32

Gnomad AFR AF: 0.806

Gnomad AMI AF: 0.517

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.542

Gnomad EAS AF: 0.667

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.517

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

GnomAD4 genome AF: 0.574 AC: 87180 AN: 151994 Hom.: 26889 Cov.: 32 AF XY: 0.570 AC XY: 42382 AN XY: 74298

African (AFR) AF: 0.806 AC: 33430 AN: 41458

American (AMR) AF: 0.416 AC: 6346 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.542 AC: 1878 AN: 3466

East Asian (EAS) AF: 0.666 AC: 3431 AN: 5152

South Asian (SAS) AF: 0.539 AC: 2596 AN: 4812

European-Finnish (FIN) AF: 0.508 AC: 5363 AN: 10564

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.478 AC: 32454 AN: 67966

Other (OTH) AF: 0.519 AC: 1093 AN: 2108

Alfa AF: 0.540 Hom.: 4815

Bravo AF: 0.575

Asia WGS AF: 0.596 AC: 2071 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.77
DANN	Benign	0.34
PhyloP100		-0.45
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: rs17601876; hg19: chr15-51553909;