dbSNP rs1143704: CYP19A1:c.743+36A>T (chr15-51218505-T-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

17 publications found

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:

MIR4713HG (HGNC:53124): (MIR4713 host gene)

MIR4713HG links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000103.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CYP19A1	NM_000103.4	MANE Select	c.743+36A>T	intron	N/A	NP_000094.2
CYP19A1	NM_001347248.1		c.743+36A>T	intron	N/A	NP_001334177.1	P11511-1
CYP19A1	NM_001347249.2		c.743+36A>T	intron	N/A	NP_001334178.1	P11511-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CYP19A1	ENST00000396402.6	TSL:1 MANE Select	c.743+36A>T	intron	N/A	ENSP00000379683.1	P11511-1
CYP19A1	ENST00000559878.5	TSL:1	c.743+36A>T	intron	N/A	ENSP00000453149.1	P11511-1
CYP19A1	ENST00000478421.1	TSL:1	n.44A>T	non_coding_transcript_exon	Exon 1 of 2

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

GnomAD2 exomes

AF:

0.450

AC:

97867

AN:

217604

AF XY:

0.455

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 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

African (AFR)

AF:

0.228

AC:

7483

AN:

32822

American (AMR)

AF:

0.327

AC:

13792

AN:

42152

Ashkenazi Jewish (ASJ)

AF:

0.531

AC:

13605

AN:

25614

East Asian (EAS)

AF:

0.475

AC:

18429

AN:

38832

South Asian (SAS)

AF:

0.359

AC:

29808

AN:

82988

European-Finnish (FIN)

AF:

0.501

AC:

26010

AN:

51914

Middle Eastern (MID)

AF:

0.420

AC:

2150

AN:

5116

European-Non Finnish (NFE)

AF:

0.528

AC:

579676

AN:

1098416

Other (OTH)

AF:

0.483

AC:

28638

AN:

59346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

17292

34584

51876

69168

86460

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16500

33000

49500

66000

82500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.423

AC:

64382

AN:

152030

Hom.:

14716

Cov.:

AF XY:

0.420

AC XY:

31179

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.242

AC:

10013

AN:

41452

American (AMR)

AF:

0.371

AC:

5672

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.540

AC:

1875

AN:

3472

East Asian (EAS)

AF:

0.497

AC:

2565

AN:

5162

South Asian (SAS)

AF:

0.362

AC:

1740

AN:

4808

European-Finnish (FIN)

AF:

0.494

AC:

5224

AN:

10580

Middle Eastern (MID)

AF:

0.425

AC:

125

AN:

294

European-Non Finnish (NFE)

AF:

0.526

AC:

35757

AN:

67956

Other (OTH)

AF:

0.442

AC:

936

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1851

3702

5552

7403

9254

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

594

1188

1782

2376

2970

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.57

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.75

CADD

Benign

6.3

(source)

DANN

Benign

0.83

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.46

MetaRNN

Benign

0.000041

PhyloP100

-0.18

GERP RS

-3.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over