6-109789584-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_014845.6(FIG4):​c.2097-10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000492 in 1,606,554 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000053 ( 1 hom. )

Consequence

FIG4
NM_014845.6 intron

Scores

2
Splicing: ADA: 0.00004359
2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.81

Publications

1 publications found
Variant links:
Genes affected
FIG4 (HGNC:16873): (FIG4 phosphoinositide 5-phosphatase) The protein encoded by this gene belongs to the SAC domain-containing protein gene family. The SAC domain, approximately 400 amino acids in length and consisting of seven conserved motifs, has been shown to possess phosphoinositide phosphatase activity. The yeast homolog, Sac1p, is involved in the regulation of various phosphoinositides, and affects diverse cellular functions such as actin cytoskeleton organization, Golgi function, and maintenance of vacuole morphology. Membrane-bound phosphoinositides function as signaling molecules and play a key role in vesicle trafficking in eukaryotic cells. Mutations in this gene have been associated with Charcot-Marie-Tooth disease, type 4J. [provided by RefSeq, Jul 2008]
FIG4 Gene-Disease associations (from GenCC):
  • Charcot-Marie-Tooth disease
    Inheritance: AR Classification: DEFINITIVE Submitted by: Illumina, ClinGen
  • Charcot-Marie-Tooth disease type 4J
    Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
  • amyotrophic lateral sclerosis type 11
    Inheritance: AD, Unknown Classification: STRONG, LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
  • Yunis-Varon syndrome
    Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet
  • amyotrophic lateral sclerosis
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • bilateral parasagittal parieto-occipital polymicrogyria
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
Variant 6-109789584-C-T is Benign according to our data. Variant chr6-109789584-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 696058.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014845.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
FIG4
NM_014845.6
MANE Select
c.2097-10C>T
intron
N/ANP_055660.1Q92562

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
FIG4
ENST00000230124.8
TSL:1 MANE Select
c.2097-10C>T
intron
N/AENSP00000230124.4Q92562
FIG4
ENST00000674884.1
c.2115-10C>T
intron
N/AENSP00000502668.1A0A6Q8PHH5
FIG4
ENST00000674744.1
c.2091-10C>T
intron
N/AENSP00000501661.1A0A6Q8PF62

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152160
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000119
AC:
3
AN:
251282
AF XY:
0.0000147
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000529
AC:
77
AN:
1454394
Hom.:
1
Cov.:
29
AF XY:
0.0000511
AC XY:
37
AN XY:
724098
show subpopulations
African (AFR)
AF:
0.0000300
AC:
1
AN:
33310
American (AMR)
AF:
0.00
AC:
0
AN:
44706
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26046
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39552
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86084
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53362
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5748
European-Non Finnish (NFE)
AF:
0.0000651
AC:
72
AN:
1105496
Other (OTH)
AF:
0.0000666
AC:
4
AN:
60090
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.455
Heterozygous variant carriers
0
3
7
10
14
17
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
4
8
12
16
20
<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:
0.0000131
AC:
2
AN:
152160
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74326
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41444
American (AMR)
AF:
0.00
AC:
0
AN:
15276
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3464
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5202
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4826
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10604
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.0000294
AC:
2
AN:
68026
Other (OTH)
AF:
0.00
AC:
0
AN:
2092
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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:
0.00
Hom.:
0
Bravo
AF:
0.0000189

ClinVar

ClinVar submissions
Significance:Likely benign
Revision:criteria provided, multiple submitters, no conflicts
View on ClinVar
Pathogenic
VUS
Benign
Condition
-
-
1
Charcot-Marie-Tooth disease (1)
-
-
1
Charcot-Marie-Tooth disease type 4 (1)

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.76
CADD
Benign
1.2
DANN
Benign
0.67
PhyloP100
-1.8

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000044
dbscSNV1_RF
Benign
0.0020
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

Other links and lift over

dbSNP: rs142482745; hg19: chr6-110110787; API
For research and educational, non-commercial use only. Not for clinical or diagnostic use. GeneBe does not provide medical advice. Data use for AI modeling is prohibited: if used, the cost is $0.001 per byte of downloaded uncompressed data.