Variant 15-51215585-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000103.4(CYP19A1):c.858+118A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 1,575,414 control chromosomes in the GnomAD database, including 200,801 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 15020 hom., cov: 32)

Exomes 𝑓: 0.51 ( 185781 hom. )

Consequence

CYP19A1
NM_000103.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.739

Variant links:

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]

CYP19A1 links:

CYP19A1 (HGNC:):

CYP19A1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 15-51215585-T-G is Benign according to our data. Variant chr15-51215585-T-G is described in ClinVar as [Benign]. Clinvar id is 1279539.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
CYP19A1	NM_000103.4 linkuse as main transcript	c.858+118A>C		intron_variant		ENST00000396402.6	NP_000094.2	P11511-1A0A024R5S8Q8IYG4Q8TCA4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP19A1	ENST00000396402.6 linkuse as main transcript	c.858+118A>C		intron_variant		1	NM_000103.4	ENSP00000379683.1		P11511-1

Frequencies

GnomAD3 genomes

AF:

0.427

AC:

64745

AN:

151766

Hom.:

15021

Cov.:

show subpopulations

Gnomad AFR

AF:

0.233

Gnomad AMI

AF:

0.524

Gnomad AMR

AF:

0.373

Gnomad ASJ

AF:

0.565

Gnomad EAS

AF:

0.511

Gnomad SAS

AF:

0.395

Gnomad FIN

AF:

0.525

Gnomad MID

AF:

0.430

Gnomad NFE

AF:

0.528

Gnomad OTH

AF:

0.450

GnomAD4 exome

AF:

0.506

AC:

720329

AN:

1423530

Hom.:

185781

AF XY:

0.504

AC XY:

355690

AN XY:

705958

show subpopulations

Gnomad4 AFR exome

AF:

0.220

Gnomad4 AMR exome

AF:

0.333

Gnomad4 ASJ exome

AF:

0.557

Gnomad4 EAS exome

AF:

0.479

Gnomad4 SAS exome

AF:

0.388

Gnomad4 FIN exome

AF:

0.528

Gnomad4 NFE exome

AF:

0.530

Gnomad4 OTH exome

AF:

0.488

GnomAD4 genome

AF:

0.426

AC:

64758

AN:

151884

Hom.:

15020

Cov.:

AF XY:

0.425

AC XY:

31519

AN XY:

74218

show subpopulations

Gnomad4 AFR

AF:

0.233

Gnomad4 AMR

AF:

0.372

Gnomad4 ASJ

AF:

0.565

Gnomad4 EAS

AF:

0.510

Gnomad4 SAS

AF:

0.397

Gnomad4 FIN

AF:

0.525

Gnomad4 NFE

AF:

0.528

Gnomad4 OTH

AF:

0.448

Alfa

AF:

0.360

Hom.:

1092

Bravo

AF:

0.409

Asia WGS

AF:

0.387

AC:

1347

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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

-0.86

CADD

Benign

0.50

DANN

Benign

0.74

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over