rs12900137

Variant names:

• chr15-51307156-G-C
• rs12900137
• NM_000103.4:c.-39+31339C>G

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+31339C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,058 control chromosomes in the GnomAD database, including 3,457 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 0.15 (3457 hom., cov: 32)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.227
• Publications: 6 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP19A1	NM_000103.4	c.-39+31339C>G		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+31339C>G		intron_variant	Intron 1 of 9	1	NM_000103.4	ENSP00000379683.1

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23492 AN: 151942 Hom.: 3438 Cov.: 32

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.00440

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.0542

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.0778

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0432

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.155 AC: 23566 AN: 152058 Hom.: 3457 Cov.: 32 AF XY: 0.158 AC XY: 11741 AN XY: 74346

African (AFR) AF: 0.378 AC: 15656 AN: 41372

American (AMR) AF: 0.115 AC: 1754 AN: 15290

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

East Asian (EAS) AF: 0.171 AC: 887 AN: 5178

South Asian (SAS) AF: 0.215 AC: 1034 AN: 4820

European-Finnish (FIN) AF: 0.0778 AC: 824 AN: 10592

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0431 AC: 2934 AN: 68020

Other (OTH) AF: 0.127 AC: 268 AN: 2116

Alfa AF: 0.108 Hom.: 250

Bravo AF: 0.166

Asia WGS AF: 0.247 AC: 860 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.6
DANN	Benign	0.65
PhyloP100		0.23
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: rs12900137; hg19: chr15-51599353;