chr15-51270895-T-G

Variant names:

• chr15-51270895-T-G
• rs11636639
• NM_000103.4:c.-38-27945A>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.-38-27945A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 151,900 control chromosomes in the GnomAD database, including 14,702 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 (14702 hom., cov: 31)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.234
• Publications: 8 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=-0.89).
• 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.-38-27945A>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.-38-27945A>C		intron_variant	Intron 1 of 9	1	NM_000103.4	ENSP00000379683.1

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66488 AN: 151782 Hom.: 14702 Cov.: 31

Gnomad AFR AF: 0.463

Gnomad AMI AF: 0.485

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.495

Gnomad EAS AF: 0.449

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.438

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

GnomAD4 genome AF: 0.438 AC: 66513 AN: 151900 Hom.: 14702 Cov.: 31 AF XY: 0.432 AC XY: 32094 AN XY: 74224

African (AFR) AF: 0.462 AC: 19158 AN: 41444

American (AMR) AF: 0.362 AC: 5525 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.495 AC: 1718 AN: 3468

East Asian (EAS) AF: 0.448 AC: 2303 AN: 5142

South Asian (SAS) AF: 0.347 AC: 1668 AN: 4802

European-Finnish (FIN) AF: 0.428 AC: 4505 AN: 10526

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

European-Non Finnish (NFE) AF: 0.444 AC: 30169 AN: 67924

Other (OTH) AF: 0.434 AC: 918 AN: 2114

Alfa AF: 0.452 Hom.: 6709

Bravo AF: 0.435

Asia WGS AF: 0.366 AC: 1272 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.6
DANN	Benign	0.64
PhyloP100		-0.23
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: rs11636639; hg19: chr15-51563092;