chr15-51269131-T-G

Variant names:

• chr15-51269131-T-G
• rs8039089
• NM_000103.4:c.-38-26181A>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.-38-26181A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 151,904 control chromosomes in the GnomAD database, including 14,657 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 0.44 (14657 hom., cov: 31)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.207
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP19A1	NM_000103.4	c.-38-26181A>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.-38-26181A>C		intron_variant	Intron 1 of 9	1	NM_000103.4	ENSP00000379683.1

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66344 AN: 151786 Hom.: 14657 Cov.: 31

Gnomad AFR AF: 0.463

Gnomad AMI AF: 0.485

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.495

Gnomad EAS AF: 0.448

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.426

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.437

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

GnomAD4 genome AF: 0.437 AC: 66369 AN: 151904 Hom.: 14657 Cov.: 31 AF XY: 0.432 AC XY: 32044 AN XY: 74248

African (AFR) AF: 0.462 AC: 19145 AN: 41416

American (AMR) AF: 0.361 AC: 5512 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.495 AC: 1719 AN: 3470

East Asian (EAS) AF: 0.447 AC: 2315 AN: 5174

South Asian (SAS) AF: 0.346 AC: 1661 AN: 4806

European-Finnish (FIN) AF: 0.426 AC: 4484 AN: 10524

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.443 AC: 30071 AN: 67924

Other (OTH) AF: 0.434 AC: 913 AN: 2106

Alfa AF: 0.451 Hom.: 2519

Bravo AF: 0.434

Asia WGS AF: 0.366 AC: 1268 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.65
PhyloP100		-0.21
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: rs8039089; hg19: chr15-51561328;