5-132863250-C-T

Position:

• chr5-132863250-C-T

Variant summary

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

The NM_005260.7(GDF9):​c.398-694G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 152,114 control chromosomes in the GnomAD database, including 2,538 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 0.17 (2538 hom., cov: 32)
• Consequence: GDF9 NM_005260.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.193

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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GDF9	NM_005260.7	c.398-694G>A		intron_variant		ENST00000687138.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GDF9	ENST00000687138.1	c.398-694G>A		intron_variant			NM_005260.7	P2

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25937 AN: 151996 Hom.: 2536 Cov.: 32

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.0538

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.163

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

GnomAD4 genome AF: 0.171 AC: 25964 AN: 152114 Hom.: 2538 Cov.: 32 AF XY: 0.168 AC XY: 12512 AN XY: 74362

Gnomad4 AFR AF: 0.266

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.117

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.161

Alfa AF: 0.159 Hom.: 263

Bravo AF: 0.172

Asia WGS AF: 0.143 AC: 501 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.7
DANN	Benign	0.63

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: rs4705974; hg19: chr5-132198942;