rs2470144

Positions:

• chr15-51329528-T-C
• chr15-51329528-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000103.4(CYP19A1):​c.-39+8967A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 152,040 control chromosomes in the GnomAD database, including 29,258 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 0.60 (29258 hom., cov: 32)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.28

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP19A1	NM_000103.4	c.-39+8967A>G		intron_variant		ENST00000396402.6	NP_000094.2
CYP19A1	NM_031226.3	c.-147-5604A>G		intron_variant			NP_112503.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP19A1	ENST00000396402.6	c.-39+8967A>G		intron_variant		1	NM_000103.4	ENSP00000379683	P1

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90681 AN: 151920 Hom.: 29186 Cov.: 32

Gnomad AFR AF: 0.852

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.594

Gnomad ASJ AF: 0.449

Gnomad EAS AF: 0.591

Gnomad SAS AF: 0.545

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.572

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

GnomAD4 genome AF: 0.597 AC: 90817 AN: 152040 Hom.: 29258 Cov.: 32 AF XY: 0.591 AC XY: 43937 AN XY: 74292

Gnomad4 AFR AF: 0.852

Gnomad4 AMR AF: 0.595

Gnomad4 ASJ AF: 0.449

Gnomad4 EAS AF: 0.592

Gnomad4 SAS AF: 0.545

Gnomad4 FIN AF: 0.399

Gnomad4 NFE AF: 0.488

Gnomad4 OTH AF: 0.574

Alfa AF: 0.497 Hom.: 27543

Bravo AF: 0.629

Asia WGS AF: 0.602 AC: 2091 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.25
DANN	Benign	0.57

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

Publications

LitVar

Other links and lift over

dbSNP: rs2470144; hg19: chr15-51621725;