rs2899472

Variant names:

• chr15-51223858-C-A
• rs2899472
• NM_000103.4:c.452-1333G>T

Your query was ambiguous. Multiple possible variants found:

• chr15-51223858-C-A
• chr15-51223858-C-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.452-1333G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 151,944 control chromosomes in the GnomAD database, including 3,051 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency: Genomes: 𝑓 0.17 (3051 hom., cov: 31)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -0.259
• Publications: 48 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.248 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.452-1333G>T		intron	N/A	NP_000094.2
	CYP19A1	NM_001347248.1		c.452-1333G>T		intron	N/A	NP_001334177.1	P11511-1
	CYP19A1	NM_001347249.2		c.452-1333G>T		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.452-1333G>T		intron	N/A	ENSP00000379683.1	P11511-1
	CYP19A1	ENST00000559878.5	TSL:1	c.452-1333G>T		intron	N/A	ENSP00000453149.1	P11511-1
	CYP19A1	ENST00000405913.7	TSL:1	c.452-1333G>T		intron	N/A	ENSP00000383930.3	P11511-2

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26311 AN: 151826 Hom.: 3048 Cov.: 31

Gnomad AFR AF: 0.0474

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.00656

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.210

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

GnomAD4 genome AF: 0.173 AC: 26317 AN: 151944 Hom.: 3051 Cov.: 31 AF XY: 0.169 AC XY: 12571 AN XY: 74238

African (AFR) AF: 0.0473 AC: 1961 AN: 41462

American (AMR) AF: 0.151 AC: 2306 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.364 AC: 1264 AN: 3470

East Asian (EAS) AF: 0.00599 AC: 31 AN: 5174

South Asian (SAS) AF: 0.150 AC: 720 AN: 4798

European-Finnish (FIN) AF: 0.214 AC: 2253 AN: 10540

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.252 AC: 17083 AN: 67918

Other (OTH) AF: 0.207 AC: 437 AN: 2110

Alfa AF: 0.228 Hom.: 17340

Bravo AF: 0.163

Asia WGS AF: 0.0690 AC: 241 AN: 3478

ClinVar

ClinVar submissions

Significance: association

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Pulmonary disease, chronic obstructive, susceptibility to (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.57
DANN	Benign	0.75
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: rs2899472; hg19: chr15-51516055;