rs10046

Variant names:

• chr15-51210789-G-A
• rs10046
• NM_000103.4:c.*19C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-51210789-G-A
• chr15-51210789-G-C
• chr15-51210789-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000103.4(CYP19A1):​c.*19C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 1,434,492 control chromosomes in the GnomAD database, including 171,911 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (14973 hom., cov: 32)
  • Exomes 𝑓: 0.49 (156938 hom.)
• Consequence: CYP19A1 NM_000103.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7 O:1
• Conservation: PhyloP100: -0.452
• Publications: 220 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 15-51210789-G-A is Benign according to our data. Variant chr15-51210789-G-A is described in ClinVar as Benign. ClinVar VariationId is 316469.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.522 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.*19C>T		3_prime_UTR	Exon 10 of 10	NP_000094.2
	CYP19A1	NM_001347248.1		c.*19C>T		3_prime_UTR	Exon 10 of 10	NP_001334177.1
	CYP19A1	NM_001347249.2		c.*19C>T		3_prime_UTR	Exon 10 of 10	NP_001334178.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP19A1	ENST00000396402.6	TSL:1 MANE Select	c.*19C>T		3_prime_UTR	Exon 10 of 10	ENSP00000379683.1
	CYP19A1	ENST00000559878.5	TSL:1	c.*19C>T		3_prime_UTR	Exon 9 of 9	ENSP00000453149.1
	CYP19A1	ENST00000396404.8	TSL:2	c.*19C>T		3_prime_UTR	Exon 11 of 11	ENSP00000379685.4

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64910 AN: 151904 Hom.: 14970 Cov.: 32

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.526

Gnomad OTH AF: 0.447

GnomAD2 exomes AF: 0.451 AC: 113281 AN: 251058 AF XY: 0.455

Gnomad AFR exome AF: 0.249

Gnomad AMR exome AF: 0.317

Gnomad ASJ exome AF: 0.534

Gnomad EAS exome AF: 0.518

Gnomad FIN exome AF: 0.529

Gnomad NFE exome AF: 0.519

Gnomad OTH exome AF: 0.485

GnomAD4 exome AF: 0.487 AC: 624570 AN: 1282470 Hom.: 156938 Cov.: 19 AF XY: 0.485 AC XY: 313680 AN XY: 647102

African (AFR) AF: 0.230 AC: 7039 AN: 30578

American (AMR) AF: 0.327 AC: 14579 AN: 44518

Ashkenazi Jewish (ASJ) AF: 0.540 AC: 13512 AN: 25010

East Asian (EAS) AF: 0.476 AC: 18547 AN: 38926

South Asian (SAS) AF: 0.334 AC: 27746 AN: 83010

European-Finnish (FIN) AF: 0.528 AC: 28154 AN: 53332

Middle Eastern (MID) AF: 0.414 AC: 2240 AN: 5412

European-Non Finnish (NFE) AF: 0.514 AC: 486903 AN: 947160

Other (OTH) AF: 0.474 AC: 25850 AN: 54524

GnomAD4 genome AF: 0.427 AC: 64934 AN: 152022 Hom.: 14973 Cov.: 32 AF XY: 0.424 AC XY: 31526 AN XY: 74284

African (AFR) AF: 0.249 AC: 10324 AN: 41488

American (AMR) AF: 0.374 AC: 5703 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.551 AC: 1911 AN: 3466

East Asian (EAS) AF: 0.498 AC: 2571 AN: 5166

South Asian (SAS) AF: 0.334 AC: 1606 AN: 4808

European-Finnish (FIN) AF: 0.523 AC: 5533 AN: 10578

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.526 AC: 35749 AN: 67934

Other (OTH) AF: 0.445 AC: 941 AN: 2114

Alfa AF: 0.491 Hom.: 55754

Bravo AF: 0.413

Asia WGS AF: 0.372 AC: 1293 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)
-	-	1	Aromatase deficiency (1)
-	-	1	Aromatase excess syndrome (1)
-	-	-	Letrozole response (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.62
DANN	Benign	0.31
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: rs10046; hg19: chr15-51502986; COSMIC: COSV53058010; COSMIC: COSV53058010;