rs17003221

Positions:

chrX-50916280-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005448.2(BMP15):c.852C>T(p.Ser284=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.034 in 1,204,453 control chromosomes in the GnomAD database, including 4,695 homozygotes. There are 12,892 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 2306 hom., 4061 hem., cov: 22)

Exomes 𝑓: 0.024 ( 2389 hom. 8831 hem. )

Consequence

BMP15
NM_005448.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.249

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant X-50916280-C-T is Benign according to our data. Variant chrX-50916280-C-T is described in ClinVar as [Benign]. Clinvar id is 259777.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.249 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.44 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.852C>T	p.Ser284=	synonymous_variant	2/2	ENST00000252677.4	NP_005439.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMP15	ENST00000252677.4 linkuse as main transcript	c.852C>T	p.Ser284=	synonymous_variant	2/2	1	NM_005448.2	ENSP00000252677	P1

Frequencies

GnomAD3 genomes

AF:

0.136

AC:

15016

AN:

110635

Hom.:

2307

Cov.:

AF XY:

0.123

AC XY:

4052

AN XY:

32901

show subpopulations

Gnomad AFR

AF:

0.447

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0601

Gnomad ASJ

AF:

0.0194

Gnomad EAS

AF:

0.0654

Gnomad SAS

AF:

0.0910

Gnomad FIN

AF:

0.000335

Gnomad MID

AF:

0.0591

Gnomad NFE

AF:

0.00477

Gnomad OTH

AF:

0.104

GnomAD3 exomes

AF:

0.0581

AC:

10426

AN:

179550

Hom.:

1147

AF XY:

0.0490

AC XY:

3154

AN XY:

64306

show subpopulations

Gnomad AFR exome

AF:

0.457

Gnomad AMR exome

AF:

0.0422

Gnomad ASJ exome

AF:

0.0200

Gnomad EAS exome

AF:

0.0652

Gnomad SAS exome

AF:

0.0972

Gnomad FIN exome

AF:

0.0000635

Gnomad NFE exome

AF:

0.00437

Gnomad OTH exome

AF:

0.0381

GnomAD4 exome

AF:

0.0237

AC:

25942

AN:

1093762

Hom.:

2389

Cov.:

AF XY:

0.0246

AC XY:

8831

AN XY:

359690

show subpopulations

Gnomad4 AFR exome

AF:

0.449

Gnomad4 AMR exome

AF:

0.0454

Gnomad4 ASJ exome

AF:

0.0189

Gnomad4 EAS exome

AF:

0.0699

Gnomad4 SAS exome

AF:

0.100

Gnomad4 FIN exome

AF:

0.000124

Gnomad4 NFE exome

AF:

0.00293

Gnomad4 OTH exome

AF:

0.0445

GnomAD4 genome

AF:

0.136

AC:

15023

AN:

110691

Hom.:

2306

Cov.:

AF XY:

0.123

AC XY:

4061

AN XY:

32967

show subpopulations

Gnomad4 AFR

AF:

0.446

Gnomad4 AMR

AF:

0.0603

Gnomad4 ASJ

AF:

0.0194

Gnomad4 EAS

AF:

0.0647

Gnomad4 SAS

AF:

0.0897

Gnomad4 FIN

AF:

0.000335

Gnomad4 NFE

AF:

0.00477

Gnomad4 OTH

AF:

0.103

Alfa

AF:

0.0384

Hom.:

1140

Bravo

AF:

0.155

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 29, 2015	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Ovarian dysgenesis 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.25

DANN

Benign

0.40

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

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