rs12908960

Variant names:

• chr15-51253663-G-A
• rs12908960
• NM_000103.4:c.-38-10713C>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.-38-10713C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 151,988 control chromosomes in the GnomAD database, including 10,799 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 0.35 (10799 hom., cov: 31)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.316
• 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]

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.453 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.-38-10713C>T		intron	N/A	NP_000094.2
	CYP19A1	NM_001347248.1		c.-38-10713C>T		intron	N/A	NP_001334177.1
	CYP19A1	NM_001347249.2		c.-38-10713C>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.-38-10713C>T		intron	N/A	ENSP00000379683.1
	CYP19A1	ENST00000439712.6	TSL:1	n.-39+1855C>T		intron	N/A	ENSP00000390614.2
	CYP19A1	ENST00000557934.5	TSL:1	n.-38-10713C>T		intron	N/A	ENSP00000454004.1

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52520 AN: 151870 Hom.: 10799 Cov.: 31

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.484

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.479

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.352

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

GnomAD4 genome AF: 0.346 AC: 52525 AN: 151988 Hom.: 10799 Cov.: 31 AF XY: 0.345 AC XY: 25642 AN XY: 74276

African (AFR) AF: 0.124 AC: 5155 AN: 41464

American (AMR) AF: 0.309 AC: 4713 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.479 AC: 1663 AN: 3470

East Asian (EAS) AF: 0.418 AC: 2154 AN: 5158

South Asian (SAS) AF: 0.298 AC: 1434 AN: 4812

European-Finnish (FIN) AF: 0.481 AC: 5079 AN: 10556

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.457 AC: 31061 AN: 67958

Other (OTH) AF: 0.347 AC: 731 AN: 2106

Alfa AF: 0.418 Hom.: 5168

Bravo AF: 0.324

Asia WGS AF: 0.289 AC: 1003 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.7
DANN	Benign	0.61
PhyloP100		0.32
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: rs12908960; hg19: chr15-51545860;