15-51303584-T-G

Variant names:

• chr15-51303584-T-G
• rs16964254
• NM_000103.4:c.-39+34911A>C

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+34911A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 151,730 control chromosomes in the GnomAD database, including 5,883 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 0.20 (5883 hom., cov: 32)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.368
• Publications: 4 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=-0.7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.488 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.-39+34911A>C		intron	N/A	NP_000094.2
	CYP19A1	NM_001347248.1		c.-39+20232A>C		intron	N/A	NP_001334177.1
	CYP19A1	NM_001347249.2		c.-39+14849A>C		intron	N/A	NP_001334178.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP19A1	ENST00000396402.6	TSL:1 MANE Select	c.-39+34911A>C		intron	N/A	ENSP00000379683.1
	CYP19A1	ENST00000439712.6	TSL:1	n.-283+34911A>C		intron	N/A	ENSP00000390614.2
	CYP19A1	ENST00000557934.5	TSL:1	n.-39+34911A>C		intron	N/A	ENSP00000454004.1

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29869 AN: 151610 Hom.: 5841 Cov.: 32

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.00440

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.0677

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.0808

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0474

Gnomad OTH AF: 0.148

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

GnomAD4 genome AF: 0.198 AC: 29974 AN: 151730 Hom.: 5883 Cov.: 32 AF XY: 0.200 AC XY: 14804 AN XY: 74124

African (AFR) AF: 0.493 AC: 20403 AN: 41356

American (AMR) AF: 0.132 AC: 2015 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.0677 AC: 235 AN: 3472

East Asian (EAS) AF: 0.315 AC: 1625 AN: 5160

South Asian (SAS) AF: 0.265 AC: 1273 AN: 4812

European-Finnish (FIN) AF: 0.0808 AC: 847 AN: 10486

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0474 AC: 3216 AN: 67898

Other (OTH) AF: 0.156 AC: 328 AN: 2108

Alfa AF: 0.0357 Hom.: 57

Bravo AF: 0.212

Asia WGS AF: 0.329 AC: 1145 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	12
DANN	Benign	0.90
PhyloP100		-0.37
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: rs16964254; hg19: chr15-51595781;