Variant 8-96145564-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001001557.4(GDF6):c.407-40C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0448 in 1,596,576 control chromosomes in the GnomAD database, including 1,898 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.040 ( 141 hom., cov: 32)

Exomes 𝑓: 0.045 ( 1757 hom. )

Consequence

GDF6
NM_001001557.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.105

Variant links:

Genes affected

GDF6 (HGNC:4221): (growth differentiation factor 6) 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 is required for normal formation of some bones and joints in the limbs, skull, and axial skeleton. Mutations in this gene are associated with Klippel-Feil syndrome, microphthalmia, and Leber congenital amaurosis. [provided by RefSeq, Sep 2016]

GDF6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 8-96145564-G-C is Benign according to our data. Variant chr8-96145564-G-C is described in ClinVar as [Benign]. Clinvar id is 256850.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GDF6	NM_001001557.4 link	c.407-40C>G		intron_variant		ENST00000287020.7	NP_001001557.1	Q6KF10A0A0S2A5D6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GDF6	ENST00000287020.7 link	c.407-40C>G		intron_variant		1	NM_001001557.4	ENSP00000287020.4		Q6KF10

Frequencies

GnomAD3 genomes

AF:

0.0396

AC:

6032

AN:

152208

Hom.:

141

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0296

Gnomad AMI

AF:

0.0595

Gnomad AMR

AF:

0.0449

Gnomad ASJ

AF:

0.0654

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0821

Gnomad FIN

AF:

0.0261

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.0443

Gnomad OTH

AF:

0.0550

GnomAD3 exomes

AF:

0.0433

AC:

9885

AN:

228108

Hom.:

278

AF XY:

0.0470

AC XY:

5950

AN XY:

126600

show subpopulations

Gnomad AFR exome

AF:

0.0283

Gnomad AMR exome

AF:

0.0250

Gnomad ASJ exome

AF:

0.0664

Gnomad EAS exome

AF:

0.000286

Gnomad SAS exome

AF:

0.0858

Gnomad FIN exome

AF:

0.0286

Gnomad NFE exome

AF:

0.0453

Gnomad OTH exome

AF:

0.0509

GnomAD4 exome

AF:

0.0454

AC:

65554

AN:

1444252

Hom.:

1757

Cov.:

AF XY:

0.0471

AC XY:

33825

AN XY:

718814

show subpopulations

Gnomad4 AFR exome

AF:

0.0312

Gnomad4 AMR exome

AF:

0.0272

Gnomad4 ASJ exome

AF:

0.0671

Gnomad4 EAS exome

AF:

0.000277

Gnomad4 SAS exome

AF:

0.0881

Gnomad4 FIN exome

AF:

0.0307

Gnomad4 NFE exome

AF:

0.0442

Gnomad4 OTH exome

AF:

0.0478

GnomAD4 genome

AF:

0.0396

AC:

6034

AN:

152324

Hom.:

141

Cov.:

AF XY:

0.0396

AC XY:

2950

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.0296

Gnomad4 AMR

AF:

0.0449

Gnomad4 ASJ

AF:

0.0654

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0828

Gnomad4 FIN

AF:

0.0261

Gnomad4 NFE

AF:

0.0443

Gnomad4 OTH

AF:

0.0535

Alfa

AF:

0.0297

Hom.:

Bravo

AF:

0.0388

Asia WGS

AF:

0.0320

AC:

112

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 15, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.70

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