chr15-51313211-A-G

Position:

• chr15-51313211-A-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+25284T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 152,264 control chromosomes in the GnomAD database, including 5,870 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 0.20 (5870 hom., cov: 33)
  • Exomes 𝑓: 0.042 (0 hom.)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.76

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=-0.67).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP19A1	NM_000103.4	c.-39+25284T>C		intron_variant		ENST00000396402.6	NP_000094.2
CYP19A1	NM_001347248.1	c.-39+10605T>C		intron_variant			NP_001334177.1
CYP19A1	NM_001347249.2	c.-39+5222T>C		intron_variant			NP_001334178.1
CYP19A1	NM_031226.3	c.-39+10605T>C		intron_variant			NP_112503.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP19A1	ENST00000396402.6	c.-39+25284T>C		intron_variant		1	NM_000103.4	ENSP00000379683	P1

Frequencies

GnomAD3 genomes AF: 0.197 AC: 30012 AN: 152122 Hom.: 5829 Cov.: 33

Gnomad AFR AF: 0.491

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.0674

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.0817

Gnomad MID AF: 0.105

Gnomad NFE AF: 0.0488

Gnomad OTH AF: 0.147

GnomAD4 exome AF: 0.0417 AC: 1 AN: 24 Hom.: 0 Cov.: 0 AF XY: 0.0500 AC XY: 1 AN XY: 20

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.198 AC: 30117 AN: 152240 Hom.: 5870 Cov.: 33 AF XY: 0.200 AC XY: 14889 AN XY: 74446

Gnomad4 AFR AF: 0.491

Gnomad4 AMR AF: 0.132

Gnomad4 ASJ AF: 0.0674

Gnomad4 EAS AF: 0.318

Gnomad4 SAS AF: 0.263

Gnomad4 FIN AF: 0.0817

Gnomad4 NFE AF: 0.0487

Gnomad4 OTH AF: 0.155

Alfa AF: 0.168 Hom.: 870

Bravo AF: 0.212

Asia WGS AF: 0.335 AC: 1164 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	14
DANN	Benign	0.71

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: rs16964258; hg19: chr15-51605408;