rs3764221

Variant names:

• chr15-51296650-G-A
• rs3764221
• NM_000103.4:c.-39+41845C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-51296650-G-A
• chr15-51296650-G-T

Variant summary

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

The NM_000103.4(CYP19A1):​c.-39+41845C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 151,994 control chromosomes in the GnomAD database, including 2,903 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 0.14 (2903 hom., cov: 32)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.330
• Publications: 8 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]

LOC124903493 (HGNC:):

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.337 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.-39+41845C>T		intron	N/A	NP_000094.2
	CYP19A1	NM_001347248.1		c.-39+27166C>T		intron	N/A	NP_001334177.1
	CYP19A1	NM_001347249.2		c.-39+21783C>T		intron	N/A	NP_001334178.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP19A1	ENST00000396402.6	TSL:1 MANE Select	c.-39+41845C>T		intron	N/A	ENSP00000379683.1
	CYP19A1	ENST00000439712.6	TSL:1	n.-282-40889C>T		intron	N/A	ENSP00000390614.2
	CYP19A1	ENST00000557934.5	TSL:1	n.-39+41845C>T		intron	N/A	ENSP00000454004.1

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21749 AN: 151874 Hom.: 2887 Cov.: 32

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.00440

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.0542

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.0786

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0411

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.144 AC: 21819 AN: 151994 Hom.: 2903 Cov.: 32 AF XY: 0.146 AC XY: 10879 AN XY: 74306

African (AFR) AF: 0.342 AC: 14165 AN: 41426

American (AMR) AF: 0.111 AC: 1702 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0542 AC: 188 AN: 3466

East Asian (EAS) AF: 0.170 AC: 878 AN: 5156

South Asian (SAS) AF: 0.209 AC: 1006 AN: 4816

European-Finnish (FIN) AF: 0.0786 AC: 830 AN: 10562

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0411 AC: 2793 AN: 67962

Other (OTH) AF: 0.112 AC: 237 AN: 2112

Alfa AF: 0.0562 Hom.: 129

Bravo AF: 0.153

Asia WGS AF: 0.233 AC: 811 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.66
DANN	Benign	0.73
PhyloP100		-0.33
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: rs3764221; hg19: chr15-51588847;