dbSNP rs3217422: CYP19A1:c.*2258_*2259insA (chr15-51208549-A-AT) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_000103.4(CYP19A1):c.*2258_*2259insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.46 ( 16488 hom., cov: 0)

Exomes 𝑓: 0.50 ( 0 hom. )

Consequence

CYP19A1
NM_000103.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.142

Publications

2 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 -10 ACMG points.

BP6

Variant 15-51208549-A-AT is Benign according to our data. Variant chr15-51208549-A-AT is described in ClinVar as Benign. ClinVar VariationId is 316444.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.

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.2258_2259insA	3_prime_UTR	Exon 10 of 10	NP_000094.2
CYP19A1	NM_001347248.1		c.2258_2259insA	3_prime_UTR	Exon 10 of 10	NP_001334177.1	P11511-1
CYP19A1	NM_001347249.2		c.2258_2259insA	3_prime_UTR	Exon 10 of 10	NP_001334178.1	P11511-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CYP19A1	ENST00000396402.6	TSL:1 MANE Select	c.2258_2259insA	3_prime_UTR	Exon 10 of 10	ENSP00000379683.1	P11511-1
MIR4713HG	ENST00000559909.1	TSL:4	n.195-69434_195-69433insT	intron	N/A
MIR4713HG	ENST00000805692.1		n.279-69434_279-69433insT	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.459

AC:

69620

AN:

151802

Hom.:

16487

Cov.:

show subpopulations

Gnomad AFR

AF:

0.356

Gnomad AMI

AF:

0.523

Gnomad AMR

AF:

0.386

Gnomad ASJ

AF:

0.551

Gnomad EAS

AF:

0.498

Gnomad SAS

AF:

0.333

Gnomad FIN

AF:

0.523

Gnomad MID

AF:

0.411

Gnomad NFE

AF:

0.528

Gnomad OTH

AF:

0.466

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.458

AC:

69648

AN:

151920

Hom.:

16488

Cov.:

AF XY:

0.454

AC XY:

33754

AN XY:

74276

show subpopulations

African (AFR)

AF:

0.356

AC:

14744

AN:

41432

American (AMR)

AF:

0.386

AC:

5887

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.551

AC:

1913

AN:

3472

East Asian (EAS)

AF:

0.498

AC:

2567

AN:

5156

South Asian (SAS)

AF:

0.335

AC:

1613

AN:

4818

European-Finnish (FIN)

AF:

0.523

AC:

5519

AN:

10552

Middle Eastern (MID)

AF:

0.408

AC:

120

AN:

294

European-Non Finnish (NFE)

AF:

0.528

AC:

35833

AN:

67918

Other (OTH)

AF:

0.464

AC:

975

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1881

3762

5643

7524

9405

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

634

1268

1902

2536

3170

<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:

0.507

Hom.:

2421

Bravo

AF:

0.448

Asia WGS

AF:

0.382

AC:

1329

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Aromatase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.14

Mutation Taster

=100/0

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over