rs936308

Variant names:

• chr15-51288877-C-G
• rs936308
• NM_000103.4:c.-38-45927G>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.-38-45927G>C 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 152,068 control chromosomes in the GnomAD database, including 9,683 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 (9683 hom., cov: 32)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.73
• Publications: 10 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP19A1	NM_000103.4	c.-38-45927G>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.-38-45927G>C		intron_variant	Intron 1 of 9	1	NM_000103.4	ENSP00000379683.1

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44317 AN: 151950 Hom.: 9645 Cov.: 32

Gnomad AFR AF: 0.610

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.129

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: 0.243

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

GnomAD4 genome AF: 0.292 AC: 44415 AN: 152068 Hom.: 9683 Cov.: 32 AF XY: 0.290 AC XY: 21537 AN XY: 74352

African (AFR) AF: 0.611 AC: 25297 AN: 41420

American (AMR) AF: 0.206 AC: 3155 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 448 AN: 3466

East Asian (EAS) AF: 0.321 AC: 1659 AN: 5168

South Asian (SAS) AF: 0.305 AC: 1466 AN: 4812

European-Finnish (FIN) AF: 0.145 AC: 1535 AN: 10594

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

European-Non Finnish (NFE) AF: 0.149 AC: 10152 AN: 67990

Other (OTH) AF: 0.248 AC: 525 AN: 2116

Alfa AF: 0.226 Hom.: 764

Bravo AF: 0.309

Asia WGS AF: 0.356 AC: 1238 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.15
DANN	Benign	0.42
PhyloP100		-1.7
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: rs936308; hg19: chr15-51581074;