rs2470176

Variant names:

• chr15-51291742-A-G
• rs2470176
• NM_000103.4:c.-39+46753T>C

Your query was ambiguous. Multiple possible variants found:

• chr15-51291742-A-G
• chr15-51291742-A-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+46753T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 152,016 control chromosomes in the GnomAD database, including 8,827 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 0.28 (8827 hom., cov: 32)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.191
• 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]

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP19A1	NM_000103.4	c.-39+46753T>C		intron_variant	Intron 1 of 9	ENST00000396402.6	NP_000094.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP19A1	ENST00000396402.6	c.-39+46753T>C		intron_variant	Intron 1 of 9	1	NM_000103.4	ENSP00000379683.1

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42809 AN: 151894 Hom.: 8790 Cov.: 32

Gnomad AFR AF: 0.576

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.238

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

GnomAD4 genome AF: 0.282 AC: 42903 AN: 152016 Hom.: 8827 Cov.: 32 AF XY: 0.281 AC XY: 20856 AN XY: 74318

African (AFR) AF: 0.577 AC: 23880 AN: 41416

American (AMR) AF: 0.204 AC: 3119 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 445 AN: 3466

East Asian (EAS) AF: 0.318 AC: 1634 AN: 5142

South Asian (SAS) AF: 0.305 AC: 1462 AN: 4796

European-Finnish (FIN) AF: 0.145 AC: 1532 AN: 10590

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.149 AC: 10154 AN: 68002

Other (OTH) AF: 0.243 AC: 514 AN: 2112

Alfa AF: 0.193 Hom.: 2153

Bravo AF: 0.297

Asia WGS AF: 0.354 AC: 1231 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.78
DANN	Benign	0.39
PhyloP100		-0.19
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: rs2470176; hg19: chr15-51583939;