rs11739194

Variant names:

• chr5-132865538-T-C
• rs11739194
• NM_005260.7:c.-1005A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

GDF9 Gene-Disease associations (from GenCC):

• premature ovarian failure 14

  Inheritance: AD, AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005260.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GDF9	NM_005260.7	MANE Select	c.-1005A>G		5_prime_UTR	Exon 1 of 2	NP_005251.1
	GDF9	NM_001288826.3		c.-146A>G		5_prime_UTR	Exon 2 of 4	NP_001275755.1
	GDF9	NM_001288824.4		c.-32+1061A>G		intron	N/A	NP_001275753.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GDF9	ENST00000687138.1	MANE Select	c.-1005A>G		5_prime_UTR	Exon 1 of 2	ENSP00000510441.1
	GDF9	ENST00000464378.2	TSL:2	c.-930A>G		5_prime_UTR	Exon 1 of 3	ENSP00000509893.1
	GDF9	ENST00000296875.4	TSL:5	c.-213A>G		5_prime_UTR	Exon 1 of 3	ENSP00000296875.3

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 2 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 3 AN: 6

Other (OTH) AF: 0.500 AC: 1 AN: 2

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

African (AFR) AF: 0.479 AC: 19819 AN: 41394

American (AMR) AF: 0.250 AC: 3805 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.311 AC: 1078 AN: 3464

East Asian (EAS) AF: 0.256 AC: 1321 AN: 5164

South Asian (SAS) AF: 0.254 AC: 1222 AN: 4808

European-Finnish (FIN) AF: 0.211 AC: 2230 AN: 10552

Middle Eastern (MID) AF: 0.379 AC: 110 AN: 290

European-Non Finnish (NFE) AF: 0.317 AC: 21567 AN: 67970

Other (OTH) AF: 0.354 AC: 746 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.5
DANN	Benign	0.47
PhyloP100		-0.86
PromoterAI		0.0057	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11739194; hg19: chr5-132201230;