rs2304463

chr15-51215923-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000103.4(CYP19A1):c.744-106T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.499 in 1,567,302 control chromosomes in the GnomAD database, including 200,018 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.43 (15057 hom., cov: 32)
  • Exomes 𝑓: 0.51 (184961 hom.)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.09

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 15-51215923-A-C is Benign according to our data. Variant chr15-51215923-A-C is described in ClinVar as [Benign]. Clinvar id is 1241371.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP19A1	NM_000103.4	c.744-106T>G		intron_variant		ENST00000396402.6
MIR4713HG	NR_146310.1	n.195-62060A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP19A1	ENST00000396402.6	c.744-106T>G		intron_variant		1	NM_000103.4	P1
MIR4713HG	ENST00000559909.1	n.195-62060A>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64811 AN: 151940 Hom.: 15059 Cov.: 32

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.515

Gnomad SAS AF: 0.391

Gnomad FIN AF: 0.524

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.450

GnomAD4 exome AF: 0.506 AC: 716531 AN: 1415244 Hom.: 184961 Cov.: 27 AF XY: 0.504 AC XY: 354109 AN XY: 702366

Gnomad4 AFR exome AF: 0.219

Gnomad4 AMR exome AF: 0.333

Gnomad4 ASJ exome AF: 0.557

Gnomad4 EAS exome AF: 0.492

Gnomad4 SAS exome AF: 0.388

Gnomad4 FIN exome AF: 0.527

Gnomad4 NFE exome AF: 0.530

Gnomad4 OTH exome AF: 0.490

GnomAD4 genome AF: 0.426 AC: 64823 AN: 152058 Hom.: 15057 Cov.: 32 AF XY: 0.424 AC XY: 31532 AN XY: 74306

Gnomad4 AFR AF: 0.233

Gnomad4 AMR AF: 0.372

Gnomad4 ASJ AF: 0.565

Gnomad4 EAS AF: 0.515

Gnomad4 SAS AF: 0.393

Gnomad4 FIN AF: 0.524

Gnomad4 NFE AF: 0.528

Gnomad4 OTH AF: 0.448

Alfa AF: 0.476 Hom.: 2664

Bravo AF: 0.410

Asia WGS AF: 0.393 AC: 1367 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.1
Dann	Benign	0.32

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: rs2304463; hg19: chr15-51508120; COSMIC: COSV53056973; COSMIC: COSV53056973;