15-51208722-C-T

Variant names:

• chr15-51208722-C-T
• rs989880661
• NM_000103.4:c.*2086G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000103.4(CYP19A1):​c.*2086G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 151,766 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.000020 (0 hom., cov: 30)
• Consequence: CYP19A1 NM_000103.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.02
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

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.*2086G>A		3_prime_UTR	Exon 10 of 10	NP_000094.2
	CYP19A1	NM_001347248.1		c.*2086G>A		3_prime_UTR	Exon 10 of 10	NP_001334177.1	P11511-1
	CYP19A1	NM_001347249.2		c.*2086G>A		3_prime_UTR	Exon 10 of 10	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.*2086G>A		3_prime_UTR	Exon 10 of 10	ENSP00000379683.1	P11511-1
	MIR4713HG	ENST00000559909.1	TSL:4	n.195-69261C>T		intron	N/A
	MIR4713HG	ENST00000805692.1		n.279-69261C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000198 AC: 3 AN: 151766 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000478

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.0000198 AC: 3 AN: 151766 Hom.: 0 Cov.: 30 AF XY: 0.0000270 AC XY: 2 AN XY: 74126

African (AFR) AF: 0.00 AC: 0 AN: 41290

American (AMR) AF: 0.00 AC: 0 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10528

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67952

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000491

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Aromatase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.0
DANN	Benign	0.68
PhyloP100		-1.0

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: rs989880661; hg19: chr15-51500919;