15-51256585-C-T

Position:

• chr15-51256585-C-T

Variant summary

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

The NM_000103.4(CYP19A1):​c.-38-13635G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.832 in 152,136 control chromosomes in the GnomAD database, including 52,877 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 0.83 (52877 hom., cov: 32)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.316

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.964 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP19A1	NM_000103.4	c.-38-13635G>A		intron_variant		ENST00000396402.6
MIR4713HG	NR_146310.1	n.195-21398C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP19A1	ENST00000396402.6	c.-38-13635G>A		intron_variant		1	NM_000103.4	P1
MIR4713HG	ENST00000559909.1	n.195-21398C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.832 AC: 126500 AN: 152018 Hom.: 52841 Cov.: 32

Gnomad AFR AF: 0.815

Gnomad AMI AF: 0.883

Gnomad AMR AF: 0.769

Gnomad ASJ AF: 0.882

Gnomad EAS AF: 0.987

Gnomad SAS AF: 0.790

Gnomad FIN AF: 0.852

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.841

Gnomad OTH AF: 0.840

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

GnomAD4 genome AF: 0.832 AC: 126591 AN: 152136 Hom.: 52877 Cov.: 32 AF XY: 0.831 AC XY: 61816 AN XY: 74406

Gnomad4 AFR AF: 0.814

Gnomad4 AMR AF: 0.769

Gnomad4 ASJ AF: 0.882

Gnomad4 EAS AF: 0.987

Gnomad4 SAS AF: 0.791

Gnomad4 FIN AF: 0.852

Gnomad4 NFE AF: 0.841

Gnomad4 OTH AF: 0.841

Alfa AF: 0.835 Hom.: 77368

Bravo AF: 0.825

Asia WGS AF: 0.892 AC: 3103 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.69

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: rs2414099; hg19: chr15-51548782;