Variant chr5-132862408-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005260.7(GDF9):c.546G>A(p.Glu182=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 1,613,476 control chromosomes in the GnomAD database, including 22,854 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2267 hom., cov: 32)

Exomes 𝑓: 0.16 ( 20587 hom. )

Consequence

GDF9
NM_005260.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.696

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 5-132862408-C-T is Benign according to our data. Variant chr5-132862408-C-T is described in ClinVar as [Benign]. Clinvar id is 137459.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.696 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GDF9	NM_005260.7 linkuse as main transcript	c.546G>A	p.Glu182=	synonymous_variant	2/2	ENST00000687138.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GDF9	ENST00000687138.1 linkuse as main transcript	c.546G>A	p.Glu182=	synonymous_variant	2/2		NM_005260.7	P2

Frequencies

GnomAD3 genomes

AF:

0.170

AC:

25813

AN:

152000

Hom.:

2265

Cov.:

show subpopulations

Gnomad AFR

AF:

0.203

Gnomad AMI

AF:

0.127

Gnomad AMR

AF:

0.132

Gnomad ASJ

AF:

0.151

Gnomad EAS

AF:

0.145

Gnomad SAS

AF:

0.0574

Gnomad FIN

AF:

0.154

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.171

Gnomad OTH

AF:

0.180

GnomAD3 exomes

AF:

0.141

AC:

35566

AN:

251406

Hom.:

2859

AF XY:

0.138

AC XY:

18775

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.206

Gnomad AMR exome

AF:

0.0874

Gnomad ASJ exome

AF:

0.160

Gnomad EAS exome

AF:

0.146

Gnomad SAS exome

AF:

0.0590

Gnomad FIN exome

AF:

0.146

Gnomad NFE exome

AF:

0.167

Gnomad OTH exome

AF:

0.157

GnomAD4 exome

AF:

0.164

AC:

239916

AN:

1461358

Hom.:

20587

Cov.:

AF XY:

0.162

AC XY:

117837

AN XY:

726994

show subpopulations

Gnomad4 AFR exome

AF:

0.205

Gnomad4 AMR exome

AF:

0.0935

Gnomad4 ASJ exome

AF:

0.161

Gnomad4 EAS exome

AF:

0.138

Gnomad4 SAS exome

AF:

0.0645

Gnomad4 FIN exome

AF:

0.151

Gnomad4 NFE exome

AF:

0.175

Gnomad4 OTH exome

AF:

0.167

GnomAD4 genome

AF:

0.170

AC:

25829

AN:

152118

Hom.:

2267

Cov.:

AF XY:

0.166

AC XY:

12327

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.203

Gnomad4 AMR

AF:

0.132

Gnomad4 ASJ

AF:

0.151

Gnomad4 EAS

AF:

0.145

Gnomad4 SAS

AF:

0.0577

Gnomad4 FIN

AF:

0.154

Gnomad4 NFE

AF:

0.171

Gnomad4 OTH

AF:

0.178

Alfa

AF:

0.172

Hom.:

1210

Bravo

AF:

0.171

Asia WGS

AF:

0.0990

AC:

346

AN:

3478

EpiCase

AF:

0.168

EpiControl

AF:

0.168

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 20, 2014

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

GDF9-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 18, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.49

DANN

Benign

0.50

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over