Genetic Variant NM_000103.4:c.-39+24114A>G (chr15-51314381-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000103.4(CYP19A1):c.-39+24114A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 151,680 control chromosomes in the GnomAD database, including 7,208 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 0.31 ( 7208 hom., cov: 31)

Consequence

CYP19A1
NM_000103.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.06

Publications

23 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CYP19A1	NM_000103.4 link	c.-39+24114A>G	intron_variant	Intron 1 of 9	ENST00000396402.6	NP_000094.2	P11511-1A0A024R5S8Q8IYG4Q8TCA4
CYP19A1	NM_001347248.1 link	c.-39+9435A>G	intron_variant	Intron 1 of 9		NP_001334177.1	P11511-1A0A024R5S8
CYP19A1	NM_001347249.2 link	c.-39+4052A>G	intron_variant	Intron 1 of 9		NP_001334178.1	P11511-1A0A024R5S8
CYP19A1	NM_031226.3 link	c.-39+9435A>G	intron_variant	Intron 2 of 10		NP_112503.1	P11511-1A0A024R5S8Q05CU4A8K6W3Q8TCA4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP19A1	ENST00000396402.6 link	c.-39+24114A>G		intron_variant	Intron 1 of 9	1	NM_000103.4	ENSP00000379683.1		P11511-1

Frequencies

GnomAD3 genomes

AF:

0.305

AC:

46283

AN:

151562

Hom.:

7205

Cov.:

show subpopulations

Gnomad AFR

AF:

0.317

Gnomad AMI

AF:

0.126

Gnomad AMR

AF:

0.349

Gnomad ASJ

AF:

0.296

Gnomad EAS

AF:

0.112

Gnomad SAS

AF:

0.261

Gnomad FIN

AF:

0.261

Gnomad MID

AF:

0.253

Gnomad NFE

AF:

0.316

Gnomad OTH

AF:

0.322

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

GnomAD4 genome

AF:

0.305

AC:

46305

AN:

151680

Hom.:

7208

Cov.:

AF XY:

0.303

AC XY:

22438

AN XY:

74132

show subpopulations

African (AFR)

AF:

0.317

AC:

13092

AN:

41352

American (AMR)

AF:

0.349

AC:

5326

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.296

AC:

1025

AN:

3468

East Asian (EAS)

AF:

0.112

AC:

570

AN:

5098

South Asian (SAS)

AF:

0.260

AC:

1247

AN:

4790

European-Finnish (FIN)

AF:

0.261

AC:

2745

AN:

10536

Middle Eastern (MID)

AF:

0.248

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.316

AC:

21440

AN:

67866

Other (OTH)

AF:

0.318

AC:

672

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1637

3274

4912

6549

8186

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

464

928

1392

1856

2320

<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:

0.319

Hom.:

14857

Bravo

AF:

0.316

Asia WGS

AF:

0.167

AC:

581

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.42

(source)

DANN

Benign

0.52

PhyloP100

-1.1

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over