rs11739194

Positions:

• chr5-132865538-T-C

Variant summary

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

The NM_005260.7(GDF9):​c.-1005A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 151,920 control chromosomes in the GnomAD database, including 9,580 homozygotes. 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 0.34 (9578 hom., cov: 31)
  • Exomes 𝑓: 0.43 (2 hom.)
• Consequence: GDF9 NM_005260.7 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.856

Genes affected

GDF9 (HGNC:4224): (growth differentiation factor 9) 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 each subunit of the disulfide-linked homodimer. This protein regulates ovarian function. Reduced expression of this gene may be associated with polycystic ovary syndrome and mutations in this gene may be more common in mothers of dizygotic twins. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GDF9	NM_005260.7	c.-1005A>G		5_prime_UTR_variant	1/2	ENST00000687138.1	NP_005251.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GDF9	ENST00000687138.1	c.-1005A>G		5_prime_UTR_variant	1/2		NM_005260.7	ENSP00000510441.1

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52091 AN: 151788 Hom.: 9566 Cov.: 31

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.381

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.357

GnomAD4 exome AF: 0.429 AC: 6 AN: 14 Hom.: 2 Cov.: 0 AF XY: 0.500 AC XY: 4 AN XY: 8

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.343 AC: 52141 AN: 151906 Hom.: 9578 Cov.: 31 AF XY: 0.335 AC XY: 24848 AN XY: 74224

Gnomad4 AFR AF: 0.479

Gnomad4 AMR AF: 0.250

Gnomad4 ASJ AF: 0.311

Gnomad4 EAS AF: 0.256

Gnomad4 SAS AF: 0.254

Gnomad4 FIN AF: 0.211

Gnomad4 NFE AF: 0.317

Gnomad4 OTH AF: 0.354

Alfa AF: 0.328 Hom.: 1063

Bravo AF: 0.353

Asia WGS AF: 0.247 AC: 863 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.5
DANN	Benign	0.47

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: rs11739194; hg19: chr5-132201230;