rs3759811

Variant names:

• chr15-51237068-T-C
• rs3759811
• NM_000103.4:c.146-59A>G

Your query was ambiguous. Multiple possible variants found:

• chr15-51237068-T-C
• chr15-51237068-T-A

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.146-59A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 1,594,836 control chromosomes in the GnomAD database, including 184,042 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.40 (13322 hom., cov: 33)
  • Exomes 𝑓: 0.48 (170720 hom.)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.259
• Publications: 15 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=-0.83).
• BP6: Variant 15-51237068-T-C is Benign according to our data. Variant chr15-51237068-T-C is described in ClinVar as Benign. ClinVar VariationId is 1271622.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.504 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.146-59A>G		intron	N/A	NP_000094.2
	CYP19A1	NM_001347248.1		c.146-59A>G		intron	N/A	NP_001334177.1	P11511-1
	CYP19A1	NM_001347249.2		c.146-59A>G		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.146-59A>G		intron	N/A	ENSP00000379683.1	P11511-1
	CYP19A1	ENST00000559878.5	TSL:1	c.146-59A>G		intron	N/A	ENSP00000453149.1	P11511-1
	CYP19A1	ENST00000405913.7	TSL:1	c.146-59A>G		intron	N/A	ENSP00000383930.3	P11511-2

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60468 AN: 152006 Hom.: 13323 Cov.: 33

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: 0.491

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.508

Gnomad OTH AF: 0.416

GnomAD4 exome AF: 0.481 AC: 693328 AN: 1442710 Hom.: 170720 AF XY: 0.478 AC XY: 343102 AN XY: 718214

African (AFR) AF: 0.191 AC: 6295 AN: 33006

American (AMR) AF: 0.304 AC: 13300 AN: 43822

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 13357 AN: 25954

East Asian (EAS) AF: 0.399 AC: 15712 AN: 39408

South Asian (SAS) AF: 0.335 AC: 28573 AN: 85298

European-Finnish (FIN) AF: 0.499 AC: 26453 AN: 52978

Middle Eastern (MID) AF: 0.384 AC: 2203 AN: 5734

European-Non Finnish (NFE) AF: 0.511 AC: 560114 AN: 1096836

Other (OTH) AF: 0.458 AC: 27321 AN: 59674

GnomAD4 genome AF: 0.398 AC: 60472 AN: 152126 Hom.: 13322 Cov.: 33 AF XY: 0.394 AC XY: 29320 AN XY: 74348

African (AFR) AF: 0.203 AC: 8444 AN: 41518

American (AMR) AF: 0.343 AC: 5238 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.520 AC: 1804 AN: 3472

East Asian (EAS) AF: 0.420 AC: 2169 AN: 5162

South Asian (SAS) AF: 0.338 AC: 1630 AN: 4826

European-Finnish (FIN) AF: 0.491 AC: 5191 AN: 10562

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

European-Non Finnish (NFE) AF: 0.508 AC: 34551 AN: 67976

Other (OTH) AF: 0.410 AC: 866 AN: 2112

Alfa AF: 0.414 Hom.: 5177

Bravo AF: 0.380

Asia WGS AF: 0.299 AC: 1043 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.8
DANN	Benign	0.60
PhyloP100		0.26
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: rs3759811; hg19: chr15-51529265; COSMIC: COSV53058059;