rs12687730

Positions:

• chrX-50911598-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005448.2(BMP15):​c.328+487T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0262 in 111,644 control chromosomes in the GnomAD database, including 57 homozygotes. There are 938 hemizygotes in GnomAD. 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 0.026 (57 hom., 938 hem., cov: 23)
• Consequence: BMP15 NM_005448.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0160

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMP15	NM_005448.2	c.328+487T>C		intron_variant		ENST00000252677.4	NP_005439.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMP15	ENST00000252677.4	c.328+487T>C		intron_variant		1	NM_005448.2	ENSP00000252677.3

Frequencies

GnomAD3 genomes AF: 0.0261 AC: 2915 AN: 111589 Hom.: 57 Cov.: 23 AF XY: 0.0275 AC XY: 930 AN XY: 33775

Gnomad AFR AF: 0.0700

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00808

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0509

Gnomad SAS AF: 0.0753

Gnomad FIN AF: 0.0322

Gnomad MID AF: 0.00417

Gnomad NFE AF: 0.00173

Gnomad OTH AF: 0.0160

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

GnomAD4 genome AF: 0.0262 AC: 2925 AN: 111644 Hom.: 57 Cov.: 23 AF XY: 0.0277 AC XY: 938 AN XY: 33840

Gnomad4 AFR AF: 0.0700

Gnomad4 AMR AF: 0.00807

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0505

Gnomad4 SAS AF: 0.0752

Gnomad4 FIN AF: 0.0322

Gnomad4 NFE AF: 0.00173

Gnomad4 OTH AF: 0.0197

Alfa AF: 0.0136 Hom.: 125

Bravo AF: 0.0263

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.5
DANN	Benign	0.58

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

Other links and lift over

dbSNP: rs12687730; hg19: chrX-50654598;