Variant rs254285 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_005260.7(GDF9):c.398-39G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.885 in 1,531,450 control chromosomes in the GnomAD database, including 604,352 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.89 ( 60600 hom., cov: 30)

Exomes 𝑓: 0.88 ( 543752 hom. )

Consequence

GDF9
NM_005260.7 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.469

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 5-132862595-C-G is Benign according to our data. Variant chr5-132862595-C-G is described in ClinVar as [Benign]. Clinvar id is 1232056.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.968 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GDF9	NM_005260.7 linkuse as main transcript	c.398-39G>C		intron_variant		ENST00000687138.1	NP_005251.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GDF9	ENST00000687138.1 linkuse as main transcript	c.398-39G>C		intron_variant			NM_005260.7	ENSP00000510441	P2

Frequencies

GnomAD3 genomes

AF:

0.887

AC:

134830

AN:

151984

Hom.:

60544

Cov.:

show subpopulations

Gnomad AFR

AF:

0.975

Gnomad AMI

AF:

0.918

Gnomad AMR

AF:

0.784

Gnomad ASJ

AF:

0.911

Gnomad EAS

AF:

0.556

Gnomad SAS

AF:

0.870

Gnomad FIN

AF:

0.755

Gnomad MID

AF:

0.930

Gnomad NFE

AF:

0.902

Gnomad OTH

AF:

0.888

GnomAD3 exomes

AF:

0.828

AC:

191959

AN:

231764

Hom.:

81738

AF XY:

0.840

AC XY:

106908

AN XY:

127232

show subpopulations

Gnomad AFR exome

AF:

0.979

Gnomad AMR exome

AF:

0.629

Gnomad ASJ exome

AF:

0.913

Gnomad EAS exome

AF:

0.543

Gnomad SAS exome

AF:

0.888

Gnomad FIN exome

AF:

0.754

Gnomad NFE exome

AF:

0.900

Gnomad OTH exome

AF:

0.863

GnomAD4 exome

AF:

0.884

AC:

1219690

AN:

1379350

Hom.:

543752

Cov.:

AF XY:

0.886

AC XY:

612272

AN XY:

690864

show subpopulations

Gnomad4 AFR exome

AF:

0.981

Gnomad4 AMR exome

AF:

0.649

Gnomad4 ASJ exome

AF:

0.914

Gnomad4 EAS exome

AF:

0.587

Gnomad4 SAS exome

AF:

0.891

Gnomad4 FIN exome

AF:

0.762

Gnomad4 NFE exome

AF:

0.906

Gnomad4 OTH exome

AF:

0.876

GnomAD4 genome

AF:

0.887

AC:

134945

AN:

152100

Hom.:

60600

Cov.:

AF XY:

0.878

AC XY:

65219

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.975

Gnomad4 AMR

AF:

0.783

Gnomad4 ASJ

AF:

0.911

Gnomad4 EAS

AF:

0.556

Gnomad4 SAS

AF:

0.871

Gnomad4 FIN

AF:

0.755

Gnomad4 NFE

AF:

0.902

Gnomad4 OTH

AF:

0.886

Alfa

AF:

0.896

Hom.:

11264

Bravo

AF:

0.888

Asia WGS

AF:

0.721

AC:

2511

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.30

DANN

Benign

0.56

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