chr8-96160259-G-T
Variant names:
Variant summary
Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001001557.4(GDF6):c.406+28C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0785 in 1,612,804 control chromosomes in the GnomAD database, including 5,711 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.063 ( 397 hom., cov: 33)
Exomes 𝑓: 0.080 ( 5314 hom. )
Consequence
GDF6
NM_001001557.4 intron
NM_001001557.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.20
Publications
5 publications found
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 Gene-Disease associations (from GenCC):
- Klippel-Feil syndrome 1, autosomal dominantInheritance: AD Classification: DEFINITIVE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)
- microphthalmiaInheritance: AD Classification: DEFINITIVE Submitted by: G2P
- multiple synostoses syndrome 4Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
- isolated Klippel-Feil syndromeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- Leber congenital amaurosisInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- isolated microphthalmia 4Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
- Leber congenital amaurosis 17Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
Variant 8-96160259-G-T is Benign according to our data. Variant chr8-96160259-G-T is described in ClinVar as Benign. ClinVar VariationId is 256848.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0917 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GDF6 | NM_001001557.4 | c.406+28C>A | intron_variant | Intron 1 of 1 | ENST00000287020.7 | NP_001001557.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0633 AC: 9634AN: 152200Hom.: 396 Cov.: 33 show subpopulations
GnomAD3 genomes
AF:
AC:
9634
AN:
152200
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.0624 AC: 15589AN: 249932 AF XY: 0.0629 show subpopulations
GnomAD2 exomes
AF:
AC:
15589
AN:
249932
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0801 AC: 116965AN: 1460486Hom.: 5314 Cov.: 32 AF XY: 0.0787 AC XY: 57183AN XY: 726708 show subpopulations
GnomAD4 exome
AF:
AC:
116965
AN:
1460486
Hom.:
Cov.:
32
AF XY:
AC XY:
57183
AN XY:
726708
show subpopulations
African (AFR)
AF:
AC:
778
AN:
33468
American (AMR)
AF:
AC:
2619
AN:
44720
Ashkenazi Jewish (ASJ)
AF:
AC:
1639
AN:
26132
East Asian (EAS)
AF:
AC:
1
AN:
39696
South Asian (SAS)
AF:
AC:
1381
AN:
86222
European-Finnish (FIN)
AF:
AC:
2954
AN:
53414
Middle Eastern (MID)
AF:
AC:
364
AN:
5766
European-Non Finnish (NFE)
AF:
AC:
102841
AN:
1110696
Other (OTH)
AF:
AC:
4388
AN:
60372
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.474
Heterozygous variant carriers
0
5215
10430
15645
20860
26075
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Exome Hom
Variant carriers
0
3586
7172
10758
14344
17930
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome AF: 0.0632 AC: 9633AN: 152318Hom.: 397 Cov.: 33 AF XY: 0.0601 AC XY: 4477AN XY: 74480 show subpopulations
GnomAD4 genome
AF:
AC:
9633
AN:
152318
Hom.:
Cov.:
33
AF XY:
AC XY:
4477
AN XY:
74480
show subpopulations
African (AFR)
AF:
AC:
1135
AN:
41590
American (AMR)
AF:
AC:
1064
AN:
15302
Ashkenazi Jewish (ASJ)
AF:
AC:
210
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5180
South Asian (SAS)
AF:
AC:
56
AN:
4824
European-Finnish (FIN)
AF:
AC:
517
AN:
10618
Middle Eastern (MID)
AF:
AC:
31
AN:
292
European-Non Finnish (NFE)
AF:
AC:
6370
AN:
68018
Other (OTH)
AF:
AC:
154
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.494
Heterozygous variant carriers
0
474
948
1421
1895
2369
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Genome Hom
Variant carriers
0
108
216
324
432
540
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
41
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
Oct 22, 2019
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided
- -
not specified Benign:1
-
PreventionGenetics, part of Exact Sciences
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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