Variant rs1143704 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.743+36A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 1,589,230 control chromosomes in the GnomAD database, including 198,649 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 14716 hom., cov: 32)

Exomes 𝑓: 0.50 ( 183933 hom. )

Consequence

CYP19A1
NM_000103.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.184

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=4.10286E-5).

BP6

Variant 15-51218505-T-A is Benign according to our data. Variant chr15-51218505-T-A is described in ClinVar as [Benign]. Clinvar id is 1168854.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.522 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.743+36A>T		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.743+36A>T		intron_variant		1	NM_000103.4	ENSP00000379683.1		P11511-1

Frequencies

GnomAD3 genomes

AF:

0.424

AC:

64367

AN:

151910

Hom.:

14718

Cov.:

show subpopulations

Gnomad AFR

AF:

0.242

Gnomad AMI

AF:

0.523

Gnomad AMR

AF:

0.372

Gnomad ASJ

AF:

0.540

Gnomad EAS

AF:

0.497

Gnomad SAS

AF:

0.360

Gnomad FIN

AF:

0.494

Gnomad MID

AF:

0.424

Gnomad NFE

AF:

0.526

Gnomad OTH

AF:

0.444

GnomAD3 exomes

AF:

0.450

AC:

97867

AN:

217604

Hom.:

23073

AF XY:

0.455

AC XY:

53133

AN XY:

116844

show subpopulations

Gnomad AFR exome

AF:

0.241

Gnomad AMR exome

AF:

0.315

Gnomad ASJ exome

AF:

0.523

Gnomad EAS exome

AF:

0.517

Gnomad SAS exome

AF:

0.355

Gnomad FIN exome

AF:

0.500

Gnomad NFE exome

AF:

0.521

Gnomad OTH exome

AF:

0.485

GnomAD4 exome

AF:

0.501

AC:

719591

AN:

1437200

Hom.:

183933

Cov.:

AF XY:

0.498

AC XY:

354910

AN XY:

712698

show subpopulations

Gnomad4 AFR exome

AF:

0.228

Gnomad4 AMR exome

AF:

0.327

Gnomad4 ASJ exome

AF:

0.531

Gnomad4 EAS exome

AF:

0.475

Gnomad4 SAS exome

AF:

0.359

Gnomad4 FIN exome

AF:

0.501

Gnomad4 NFE exome

AF:

0.528

Gnomad4 OTH exome

AF:

0.483

GnomAD4 genome

AF:

0.423

AC:

64382

AN:

152030

Hom.:

14716

Cov.:

AF XY:

0.420

AC XY:

31179

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.242

Gnomad4 AMR

AF:

0.371

Gnomad4 ASJ

AF:

0.540

Gnomad4 EAS

AF:

0.497

Gnomad4 SAS

AF:

0.362

Gnomad4 FIN

AF:

0.494

Gnomad4 NFE

AF:

0.526

Gnomad4 OTH

AF:

0.442

Alfa

AF:

0.491

Hom.:

3498

Bravo

AF:

0.409

TwinsUK

AF:

0.541

AC:

2007

ALSPAC

AF:

0.525

AC:

2022

ESP6500AA

AF:

0.246

AC:

1081

ESP6500EA

AF:

0.519

AC:

4452

ExAC

AF:

0.430

AC:

51739

Asia WGS

AF:

0.379

AC:

1318

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	This variant is associated with the following publications: (PMID: 16882736) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.75

CADD

Benign

6.3

DANN

Benign

0.83

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.46

MetaRNN

Benign

0.000041

GERP RS

-3.8

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