chrX-50915683-A-C

Position:

• chrX-50915683-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005448.2(BMP15):​c.329-74A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.018 in 1,166,283 control chromosomes in the GnomAD database, including 642 homozygotes. There are 7,563 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.047 (216 hom., 1483 hem., cov: 22)
  • Exomes 𝑓: 0.015 (426 hom. 6080 hem.)
• Consequence: BMP15 NM_005448.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.38

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant X-50915683-A-C is Benign according to our data. Variant chrX-50915683-A-C is described in ClinVar as [Benign]. Clinvar id is 1292837.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMP15	NM_005448.2	c.329-74A>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.329-74A>C		intron_variant		1	NM_005448.2	ENSP00000252677	P1

Frequencies

GnomAD3 genomes AF: 0.0467 AC: 5215 AN: 111700 Hom.: 216 Cov.: 22 AF XY: 0.0436 AC XY: 1477 AN XY: 33880

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0285

Gnomad ASJ AF: 0.0189

Gnomad EAS AF: 0.0671

Gnomad SAS AF: 0.0946

Gnomad FIN AF: 0.000488

Gnomad MID AF: 0.0424

Gnomad NFE AF: 0.00323

Gnomad OTH AF: 0.0391

GnomAD4 exome AF: 0.0149 AC: 15726 AN: 1054528 Hom.: 426 AF XY: 0.0185 AC XY: 6080 AN XY: 328014

Gnomad4 AFR exome AF: 0.141

Gnomad4 AMR exome AF: 0.0264

Gnomad4 ASJ exome AF: 0.0189

Gnomad4 EAS exome AF: 0.0705

Gnomad4 SAS exome AF: 0.103

Gnomad4 FIN exome AF: 0.000124

Gnomad4 NFE exome AF: 0.00251

Gnomad4 OTH exome AF: 0.0249

GnomAD4 genome AF: 0.0467 AC: 5217 AN: 111755 Hom.: 216 Cov.: 22 AF XY: 0.0437 AC XY: 1483 AN XY: 33945

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.0289

Gnomad4 ASJ AF: 0.0189

Gnomad4 EAS AF: 0.0664

Gnomad4 SAS AF: 0.0945

Gnomad4 FIN AF: 0.000488

Gnomad4 NFE AF: 0.00323

Gnomad4 OTH AF: 0.0393

Alfa AF: 0.0291 Hom.: 136

Bravo AF: 0.0546

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 31, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.29
DANN	Benign	0.45

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: rs73488037; hg19: chrX-50658683;