15-51227079-T-G

Variant names:

• chr15-51227079-T-G
• rs4775935
• NM_000103.4:c.451+700A>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.451+700A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.657 in 151,974 control chromosomes in the GnomAD database, including 32,840 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 0.66 (32840 hom., cov: 33)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.277
• Publications: 11 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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP19A1	NM_000103.4	c.451+700A>C		intron_variant	Intron 4 of 9	ENST00000396402.6	NP_000094.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP19A1	ENST00000396402.6	c.451+700A>C		intron_variant	Intron 4 of 9	1	NM_000103.4	ENSP00000379683.1

Frequencies

GnomAD3 genomes AF: 0.657 AC: 99710 AN: 151856 Hom.: 32800 Cov.: 33

Gnomad AFR AF: 0.672

Gnomad AMI AF: 0.633

Gnomad AMR AF: 0.611

Gnomad ASJ AF: 0.677

Gnomad EAS AF: 0.689

Gnomad SAS AF: 0.746

Gnomad FIN AF: 0.660

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.649

Gnomad OTH AF: 0.622

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

GnomAD4 genome AF: 0.657 AC: 99802 AN: 151974 Hom.: 32840 Cov.: 33 AF XY: 0.659 AC XY: 48958 AN XY: 74306

African (AFR) AF: 0.672 AC: 27806 AN: 41350

American (AMR) AF: 0.611 AC: 9330 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.677 AC: 2348 AN: 3468

East Asian (EAS) AF: 0.688 AC: 3560 AN: 5176

South Asian (SAS) AF: 0.746 AC: 3595 AN: 4816

European-Finnish (FIN) AF: 0.660 AC: 6991 AN: 10588

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.649 AC: 44114 AN: 67978

Other (OTH) AF: 0.623 AC: 1316 AN: 2114

Alfa AF: 0.653 Hom.: 19271

Bravo AF: 0.651

Asia WGS AF: 0.685 AC: 2384 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.5
DANN	Benign	0.61
PhyloP100		0.28
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: rs4775935; hg19: chr15-51519276;