rs936306

Variant names:

• chr15-51287401-C-T
• rs936306
• NM_000103.4:c.-38-44451G>A

Variant summary

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

The NM_000103.4(CYP19A1):​c.-38-44451G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 152,054 control chromosomes in the GnomAD database, including 9,675 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 0.29 (9675 hom., cov: 32)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.340
• Publications: 50 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.604 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.-38-44451G>A		intron	N/A	NP_000094.2
	CYP19A1	NM_001347248.1		c.-39+36415G>A		intron	N/A	NP_001334177.1	P11511-1
	CYP19A1	NM_001347249.2		c.-39+31032G>A		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.-38-44451G>A		intron	N/A	ENSP00000379683.1	P11511-1
	CYP19A1	ENST00000439712.6	TSL:1	n.-282-31640G>A		intron	N/A	ENSP00000390614.2	E7EQ08
	CYP19A1	ENST00000557934.5	TSL:1	n.-38-44451G>A		intron	N/A	ENSP00000454004.1	E7EQ08

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44314 AN: 151936 Hom.: 9637 Cov.: 32

Gnomad AFR AF: 0.610

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.292 AC: 44412 AN: 152054 Hom.: 9675 Cov.: 32 AF XY: 0.290 AC XY: 21551 AN XY: 74344

African (AFR) AF: 0.611 AC: 25302 AN: 41438

American (AMR) AF: 0.206 AC: 3153 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 444 AN: 3464

East Asian (EAS) AF: 0.321 AC: 1658 AN: 5162

South Asian (SAS) AF: 0.304 AC: 1464 AN: 4810

European-Finnish (FIN) AF: 0.145 AC: 1539 AN: 10584

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

European-Non Finnish (NFE) AF: 0.149 AC: 10149 AN: 67990

Other (OTH) AF: 0.249 AC: 525 AN: 2112

Alfa AF: 0.195 Hom.: 15689

Bravo AF: 0.308

Asia WGS AF: 0.356 AC: 1239 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.2
DANN	Benign	0.79
PhyloP100		-0.34
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: rs936306; hg19: chr15-51579598;