chr5-132865251-C-T

Variant names:

• chr5-132865251-C-T
• rs11748063
• NM_005260.7:c.-718G>A

Variant summary

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

The NM_005260.7(GDF9):​c.-718G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 152,204 control chromosomes in the GnomAD database, including 9,760 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 0.35 (9756 hom., cov: 32)
  • Exomes 𝑓: 0.22 (4 hom.)
• Consequence: GDF9 NM_005260.7 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.152

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=-0.96).
• 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 rank	MANE	Protein	UniProt
GDF9	NM_005260.7	c.-718G>A		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 2	ENST00000687138.1	NP_005251.1
GDF9	NM_005260.7	c.-718G>A		5_prime_UTR_variant	Exon 1 of 2	ENST00000687138.1	NP_005251.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GDF9	ENST00000687138.1	c.-718G>A		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 2		NM_005260.7	ENSP00000510441.1
GDF9	ENST00000687138.1	c.-718G>A		5_prime_UTR_variant	Exon 1 of 2		NM_005260.7	ENSP00000510441.1

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52861 AN: 151924 Hom.: 9745 Cov.: 32

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.267

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.381

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.360

GnomAD4 exome AF: 0.216 AC: 35 AN: 162 Hom.: 4 Cov.: 0 AF XY: 0.212 AC XY: 17 AN XY: 80

Gnomad4 AMR exome AF: 0.00

Gnomad4 SAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.229

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.348 AC: 52910 AN: 152042 Hom.: 9756 Cov.: 32 AF XY: 0.342 AC XY: 25386 AN XY: 74302

Gnomad4 AFR AF: 0.479

Gnomad4 AMR AF: 0.250

Gnomad4 ASJ AF: 0.313

Gnomad4 EAS AF: 0.262

Gnomad4 SAS AF: 0.255

Gnomad4 FIN AF: 0.266

Gnomad4 NFE AF: 0.319

Gnomad4 OTH AF: 0.357

Alfa AF: 0.321 Hom.: 12370

Bravo AF: 0.353

Asia WGS AF: 0.256 AC: 892 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.7
DANN	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11748063; hg19: chr5-132200943;