rs3810682

Variant names:

• chrX-50910775-C-A
• rs3810682
• NM_005448.2:c.-9C>A

Your query was ambiguous. Multiple possible variants found:

• chrX-50910775-C-A
• chrX-50910775-C-G
• chrX-50910775-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005448.2(BMP15):​c.-9C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000276 in 1,087,223 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 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: not found (cov: 23)
  • Exomes 𝑓: 0.0000028 (0 hom. 1 hem.)
• Consequence: BMP15 NM_005448.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• Publications: 0 publications found

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: Labcorp Genetics (formerly Invitae), Ambry Genetics
• 46 XX gonadal dysgenesis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP15	NM_005448.2	c.-9C>A		5_prime_UTR_variant	Exon 1 of 2	ENST00000252677.4	NP_005439.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMP15	ENST00000252677.4	c.-9C>A		5_prime_UTR_variant	Exon 1 of 2	1	NM_005448.2	ENSP00000252677.3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000276 AC: 3 AN: 1087223 Hom.: 0 Cov.: 31 AF XY: 0.00000282 AC XY: 1 AN XY: 354667

African (AFR) AF: 0.00 AC: 0 AN: 26191

American (AMR) AF: 0.00 AC: 0 AN: 34435

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19223

East Asian (EAS) AF: 0.00 AC: 0 AN: 30011

South Asian (SAS) AF: 0.00 AC: 0 AN: 52704

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40035

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4125

European-Non Finnish (NFE) AF: 0.00000359 AC: 3 AN: 834805

Other (OTH) AF: 0.00 AC: 0 AN: 45694

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.7
DANN	Benign	0.62
PhyloP100		-1.3
PromoterAI		-0.054	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3810682; hg19: chrX-50653775;