rs700518

Variant names:

• chr15-51236915-T-C
• rs700518
• NM_000103.4:c.240A>G

Your query was ambiguous. Multiple possible variants found:

• chr15-51236915-T-C
• chr15-51236915-T-A
• chr15-51236915-T-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000103.4(CYP19A1):​c.240A>G​(p.Val80Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 1,613,856 control chromosomes in the GnomAD database, including 186,049 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.40 (13331 hom., cov: 32)
  • Exomes 𝑓: 0.48 (172718 hom.)
• Consequence: CYP19A1 NM_000103.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.655
• Publications: 130 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 15-51236915-T-C is Benign according to our data. Variant chr15-51236915-T-C is described in ClinVar as Benign. ClinVar VariationId is 316477.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.655 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.504 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.240A>G	p.Val80Val	synonymous	Exon 3 of 10	NP_000094.2
	CYP19A1	NM_001347248.1		c.240A>G	p.Val80Val	synonymous	Exon 3 of 10	NP_001334177.1	P11511-1
	CYP19A1	NM_001347249.2		c.240A>G	p.Val80Val	synonymous	Exon 3 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.240A>G	p.Val80Val	synonymous	Exon 3 of 10	ENSP00000379683.1	P11511-1
	CYP19A1	ENST00000559878.5	TSL:1	c.240A>G	p.Val80Val	synonymous	Exon 2 of 9	ENSP00000453149.1	P11511-1
	CYP19A1	ENST00000405913.7	TSL:1	c.240A>G	p.Val80Val	synonymous	Exon 2 of 4	ENSP00000383930.3	P11511-2

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60479 AN: 151934 Hom.: 13332 Cov.: 32

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.350

Gnomad NFE AF: 0.508

Gnomad OTH AF: 0.417

GnomAD2 exomes AF: 0.426 AC: 107137 AN: 251450 AF XY: 0.432

Gnomad AFR exome AF: 0.202

Gnomad AMR exome AF: 0.293

Gnomad ASJ exome AF: 0.507

Gnomad EAS exome AF: 0.436

Gnomad FIN exome AF: 0.497

Gnomad NFE exome AF: 0.501

Gnomad OTH exome AF: 0.455

GnomAD4 exome AF: 0.480 AC: 701412 AN: 1461802 Hom.: 172718 Cov.: 63 AF XY: 0.477 AC XY: 346916 AN XY: 727204

African (AFR) AF: 0.190 AC: 6363 AN: 33478

American (AMR) AF: 0.303 AC: 13536 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.514 AC: 13440 AN: 26134

East Asian (EAS) AF: 0.399 AC: 15851 AN: 39698

South Asian (SAS) AF: 0.335 AC: 28862 AN: 86258

European-Finnish (FIN) AF: 0.499 AC: 26672 AN: 53412

Middle Eastern (MID) AF: 0.383 AC: 2209 AN: 5768

European-Non Finnish (NFE) AF: 0.510 AC: 566871 AN: 1111946

Other (OTH) AF: 0.457 AC: 27608 AN: 60388

GnomAD4 genome AF: 0.398 AC: 60485 AN: 152054 Hom.: 13331 Cov.: 32 AF XY: 0.395 AC XY: 29339 AN XY: 74316

African (AFR) AF: 0.204 AC: 8452 AN: 41498

American (AMR) AF: 0.343 AC: 5237 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.520 AC: 1803 AN: 3468

East Asian (EAS) AF: 0.421 AC: 2176 AN: 5172

South Asian (SAS) AF: 0.338 AC: 1626 AN: 4814

European-Finnish (FIN) AF: 0.492 AC: 5198 AN: 10556

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.508 AC: 34547 AN: 67944

Other (OTH) AF: 0.411 AC: 867 AN: 2110

Alfa AF: 0.468 Hom.: 82541

Bravo AF: 0.380

Asia WGS AF: 0.301 AC: 1050 AN: 3478

EpiCase AF: 0.481

EpiControl AF: 0.487

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	3.7
DANN	Benign	0.68
PhyloP100		0.66
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs700518; hg19: chr15-51529112; COSMIC: COSV53058055;