Variant X-50916210-C-CTCT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 3P and 16B. PM1PM4_SupportingBP6_Very_StrongBA1

The NM_005448.2(BMP15):c.786_788dupTCT(p.Leu263dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0338 in 1,208,442 control chromosomes in the GnomAD database, including 4,697 homozygotes. There are 12,745 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 2285 hom., 3760 hem., cov: 18)

Exomes 𝑓: 0.024 ( 2412 hom. 8985 hem. )

Consequence

BMP15
NM_005448.2 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 0.176

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

PM1

In a propeptide (size 248) in uniprot entity BMP15_HUMAN there are 8 pathogenic changes around while only 0 benign (100%) in NM_005448.2

PM4

Nonframeshift variant in NON repetitive region in NM_005448.2. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant X-50916210-C-CTCT is Benign according to our data. Variant chrX-50916210-C-CTCT is described in ClinVar as [Benign]. Clinvar id is 259775.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMP15	NM_005448.2 linkuse as main transcript	c.786_788dupTCT	p.Leu263dup	disruptive_inframe_insertion	2/2	ENST00000252677.4	NP_005439.2	O95972

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMP15	ENST00000252677.4 linkuse as main transcript	c.786_788dupTCT	p.Leu263dup	disruptive_inframe_insertion	2/2	1	NM_005448.2	ENSP00000252677.3		O95972

Frequencies

GnomAD3 genomes

AF:

0.133

AC:

14660

AN:

110247

Hom.:

2286

Cov.:

AF XY:

0.115

AC XY:

3752

AN XY:

32587

show subpopulations

Gnomad AFR

AF:

0.442

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0584

Gnomad ASJ

AF:

0.0186

Gnomad EAS

AF:

0.0638

Gnomad SAS

AF:

0.0908

Gnomad FIN

AF:

0.000500

Gnomad MID

AF:

0.0551

Gnomad NFE

AF:

0.00469

Gnomad OTH

AF:

0.102

GnomAD3 exomes

AF:

0.0577

AC:

10570

AN:

183113

Hom.:

1148

AF XY:

0.0483

AC XY:

3262

AN XY:

67603

show subpopulations

Gnomad AFR exome

AF:

0.455

Gnomad AMR exome

AF:

0.0421

Gnomad ASJ exome

AF:

0.0188

Gnomad EAS exome

AF:

0.0647

Gnomad SAS exome

AF:

0.0997

Gnomad FIN exome

AF:

0.0000625

Gnomad NFE exome

AF:

0.00424

Gnomad OTH exome

AF:

0.0380

GnomAD4 exome

AF:

0.0239

AC:

26227

AN:

1098141

Hom.:

2412

Cov.:

AF XY:

0.0247

AC XY:

8985

AN XY:

363509

show subpopulations

Gnomad4 AFR exome

AF:

0.449

Gnomad4 AMR exome

AF:

0.0451

Gnomad4 ASJ exome

AF:

0.0187

Gnomad4 EAS exome

AF:

0.0698

Gnomad4 SAS exome

AF:

0.103

Gnomad4 FIN exome

AF:

0.000123

Gnomad4 NFE exome

AF:

0.00293

Gnomad4 OTH exome

AF:

0.0446

GnomAD4 genome

AF:

0.133

AC:

14666

AN:

110301

Hom.:

2285

Cov.:

AF XY:

0.115

AC XY:

3760

AN XY:

32651

show subpopulations

Gnomad4 AFR

AF:

0.441

Gnomad4 AMR

AF:

0.0586

Gnomad4 ASJ

AF:

0.0186

Gnomad4 EAS

AF:

0.0631

Gnomad4 SAS

AF:

0.0891

Gnomad4 FIN

AF:

0.000500

Gnomad4 NFE

AF:

0.00470

Gnomad4 OTH

AF:

0.101

Alfa

AF:

0.0564

Hom.:

560

Asia WGS

AF:

0.115

AC:

294

AN:

2522

EpiCase

AF:

0.00638

EpiControl

AF:

0.00725

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 01, 2015

This variant is associated with the following publications: (PMID: 16508750, 25954833) -

Ovarian dysgenesis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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