15-51321614-T-C

Position:

• chr15-51321614-T-C

Variant summary

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

The ENST00000396402.6(CYP19A1):​c.-39+16881A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 152,120 control chromosomes in the GnomAD database, including 12,917 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 0.40 (12917 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: CYP19A1 ENST00000396402.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.607

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP19A1	NM_000103.4	c.-39+16881A>G		intron_variant		ENST00000396402.6	NP_000094.2
LOC112268146	XR_002957708.2	n.1118T>C		non_coding_transcript_exon_variant	2/2
CYP19A1	NM_001347248.1	c.-39+2202A>G		intron_variant			NP_001334177.1
CYP19A1	NM_031226.3	c.-39+2202A>G		intron_variant			NP_112503.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP19A1	ENST00000396402.6	c.-39+16881A>G		intron_variant		1	NM_000103.4	ENSP00000379683	P1
	ENST00000559672.2	n.394T>C		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61416 AN: 152000 Hom.: 12880 Cov.: 32

Gnomad AFR AF: 0.485

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.349

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.416

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.404 AC: 61503 AN: 152120 Hom.: 12917 Cov.: 32 AF XY: 0.400 AC XY: 29774 AN XY: 74356

Gnomad4 AFR AF: 0.485

Gnomad4 AMR AF: 0.464

Gnomad4 ASJ AF: 0.403

Gnomad4 EAS AF: 0.299

Gnomad4 SAS AF: 0.469

Gnomad4 FIN AF: 0.221

Gnomad4 NFE AF: 0.375

Gnomad4 OTH AF: 0.417

Alfa AF: 0.286 Hom.: 915

Bravo AF: 0.428

Asia WGS AF: 0.428 AC: 1488 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.9
DANN	Benign	0.68

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: rs1004982; hg19: chr15-51613811;