15-51321709-C-G

Position:

• chr15-51321709-C-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+16786G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.565 in 152,148 control chromosomes in the GnomAD database, including 26,944 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 0.56 (26939 hom., cov: 32)
  • Exomes 𝑓: 0.38 (5 hom.)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.429

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]

ENSG00000259306 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.836 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP19A1	NM_000103.4	c.-39+16786G>C		intron_variant		ENST00000396402.6	NP_000094.2
CYP19A1	NM_001347248.1	c.-39+2107G>C		intron_variant			NP_001334177.1
CYP19A1	NM_031226.3	c.-39+2107G>C		intron_variant			NP_112503.1
LOC112268146	XR_002957708.2	n.1213C>G		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP19A1	ENST00000396402.6	c.-39+16786G>C		intron_variant		1	NM_000103.4	ENSP00000379683.1

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85753 AN: 151938 Hom.: 26866 Cov.: 32

Gnomad AFR AF: 0.843

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.588

Gnomad ASJ AF: 0.434

Gnomad EAS AF: 0.584

Gnomad SAS AF: 0.508

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.553

GnomAD4 exome AF: 0.380 AC: 35 AN: 92 Hom.: 5 Cov.: 0 AF XY: 0.394 AC XY: 26 AN XY: 66

Gnomad4 AFR exome AF: 1.00

Gnomad4 ASJ exome AF: 0.500

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.354

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.565 AC: 85886 AN: 152056 Hom.: 26939 Cov.: 32 AF XY: 0.559 AC XY: 41509 AN XY: 74320

Gnomad4 AFR AF: 0.843

Gnomad4 AMR AF: 0.589

Gnomad4 ASJ AF: 0.434

Gnomad4 EAS AF: 0.585

Gnomad4 SAS AF: 0.507

Gnomad4 FIN AF: 0.306

Gnomad4 NFE AF: 0.443

Gnomad4 OTH AF: 0.556

Alfa AF: 0.482 Hom.: 2307

Bravo AF: 0.604

Asia WGS AF: 0.586 AC: 2036 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.6
DANN	Benign	0.77

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: rs1902585; hg19: chr15-51613906;