X-50911091-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005448.2(BMP15):c.308A>G(p.Asn103Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0708 in 1,183,664 control chromosomes in the GnomAD database, including 2,296 homozygotes. There are 27,334 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.051 ( 151 hom., 1764 hem., cov: 24)

Exomes 𝑓: 0.073 ( 2145 hom. 25570 hem. )

Consequence

BMP15
NM_005448.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.0570

Publications

18 publications found

Variant links:

Genes affected

BMP15 (HGNC:1068): (bone morphogenetic protein 15) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate subunits of a disulfide-linked homodimer, or alternatively, a heterodimer, with the related protein, growth differentiation factor 9 (GDF9). This protein plays a role in oocyte maturation and follicular development, through activation of granulosa cells. Defects in this gene are the cause of ovarian dysgenesis and are associated with premature ovarian failure. [provided by RefSeq, Aug 2016]

BMP15 Gene-Disease associations (from GenCC):

ovarian dysgenesis 2
Inheritance: XL, AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
46 XX gonadal dysgenesis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

BMP15 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=0.0018285215).

BP6

Variant X-50911091-A-G is Benign according to our data. Variant chrX-50911091-A-G is described in ClinVar as Benign. ClinVar VariationId is 136523.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0749 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005448.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP15	NM_005448.2	MANE Select	c.308A>G	p.Asn103Ser	missense	Exon 1 of 2	NP_005439.2	O95972

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP15	ENST00000252677.4	TSL:1 MANE Select	c.308A>G	p.Asn103Ser	missense	Exon 1 of 2	ENSP00000252677.3	O95972

Frequencies

GnomAD3 genomes

AF:

0.0511

AC:

5769

AN:

112834

Hom.:

151

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00967

Gnomad AMI

AF:

0.171

Gnomad AMR

AF:

0.0433

Gnomad ASJ

AF:

0.0366

Gnomad EAS

AF:

0.000563

Gnomad SAS

AF:

0.0563

Gnomad FIN

AF:

0.0760

Gnomad MID

AF:

0.0417

Gnomad NFE

AF:

0.0768

Gnomad OTH

AF:

0.0347

GnomAD2 exomes

AF:

0.0571

AC:

7747

AN:

135741

AF XY:

0.0612

show subpopulations

Gnomad AFR exome

AF:

0.00962

Gnomad AMR exome

AF:

0.0260

Gnomad ASJ exome

AF:

0.0468

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0897

Gnomad NFE exome

AF:

0.0804

Gnomad OTH exome

AF:

0.0623

GnomAD4 exome

AF:

0.0729

AC:

78070

AN:

1070775

Hom.:

2145

Cov.:

AF XY:

0.0735

AC XY:

25570

AN XY:

347937

show subpopulations

African (AFR)

AF:

0.00892

AC:

229

AN:

25682

American (AMR)

AF:

0.0263

AC:

832

AN:

31598

Ashkenazi Jewish (ASJ)

AF:

0.0458

AC:

863

AN:

18860

East Asian (EAS)

AF:

0.0000700

AC:

AN:

28574

South Asian (SAS)

AF:

0.0633

AC:

3218

AN:

50814

European-Finnish (FIN)

AF:

0.0854

AC:

3258

AN:

38162

Middle Eastern (MID)

AF:

0.0685

AC:

262

AN:

3825

European-Non Finnish (NFE)

AF:

0.0804

AC:

66629

AN:

828244

Other (OTH)

AF:

0.0617

AC:

2777

AN:

45016

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

3032

6064

9096

12128

15160

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2490

4980

7470

9960

12450

<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:

0.0511

AC:

5768

AN:

112889

Hom.:

151

Cov.:

AF XY:

0.0503

AC XY:

1764

AN XY:

35043

show subpopulations

African (AFR)

AF:

0.00965

AC:

301

AN:

31202

American (AMR)

AF:

0.0433

AC:

468

AN:

10811

Ashkenazi Jewish (ASJ)

AF:

0.0366

AC:

AN:

2652

East Asian (EAS)

AF:

0.000564

AC:

AN:

3545

South Asian (SAS)

AF:

0.0564

AC:

154

AN:

2729

European-Finnish (FIN)

AF:

0.0760

AC:

474

AN:

6236

Middle Eastern (MID)

AF:

0.0457

AC:

AN:

219

European-Non Finnish (NFE)

AF:

0.0768

AC:

4093

AN:

53270

Other (OTH)

AF:

0.0343

AC:

AN:

1547

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

198

396

593

791

989

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

210

280

350

<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:

0.0661

Hom.:

3757

Bravo

AF:

0.0470

TwinsUK

AF:

0.0779

AC:

289

ALSPAC

AF:

0.0779

AC:

225

ESP6500AA

AF:

0.0113

AC:

ESP6500EA

AF:

0.0800

AC:

535

ExAC

AF:

0.0493

AC:

5738

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (2)

Ovarian dysgenesis 2 (2)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.10

(source)

DANN

Benign

0.37

DEOGEN2

Benign

0.19

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.68

MetaRNN

Benign

0.0018

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.69

PhyloP100

-0.057

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.29

REVEL

Benign

0.12

Sift

Benign

0.71

Sift4G

Benign

0.99

Polyphen

0.0020

Vest4

0.011

MPC

0.021

ClinPred

0.0034

GERP RS

0.75

PromoterAI

-0.035

Neutral

(source)

Varity_R

0.028

gMVP

0.14

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