chr17-44915158-G-C
Variant names:
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6BS1BS2
The NM_002055.5(GFAP):āc.329C>Gā(p.Thr110Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000203 in 1,614,160 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.00022 ( 1 hom., cov: 32)
Exomes š: 0.00020 ( 3 hom. )
Consequence
GFAP
NM_002055.5 missense
NM_002055.5 missense
Scores
3
16
Clinical Significance
Conservation
PhyloP100: 6.31
Genes affected
GFAP (HGNC:4235): (glial fibrillary acidic protein) This gene encodes one of the major intermediate filament proteins of mature astrocytes. It is used as a marker to distinguish astrocytes from other glial cells during development. Mutations in this gene cause Alexander disease, a rare disorder of astrocytes in the central nervous system. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Oct 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.08596799).
BP6
Variant 17-44915158-G-C is Benign according to our data. Variant chr17-44915158-G-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 323625.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Likely_benign=2}. Variant chr17-44915158-G-C is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000223 (34/152328) while in subpopulation AMR AF= 0.000849 (13/15312). AF 95% confidence interval is 0.000502. There are 1 homozygotes in gnomad4. There are 18 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 34 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GFAP | NM_002055.5 | c.329C>G | p.Thr110Ser | missense_variant | Exon 1 of 9 | ENST00000588735.3 | NP_002046.1 | |
GFAP | NM_001363846.2 | c.329C>G | p.Thr110Ser | missense_variant | Exon 1 of 10 | NP_001350775.1 | ||
GFAP | NM_001242376.3 | c.329C>G | p.Thr110Ser | missense_variant | Exon 1 of 7 | NP_001229305.1 | ||
GFAP | NM_001131019.3 | c.329C>G | p.Thr110Ser | missense_variant | Exon 1 of 8 | NP_001124491.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000223 AC: 34AN: 152212Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000259 AC: 65AN: 251384Hom.: 0 AF XY: 0.000287 AC XY: 39AN XY: 135890
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GnomAD4 exome AF: 0.000201 AC: 294AN: 1461832Hom.: 3 Cov.: 31 AF XY: 0.000204 AC XY: 148AN XY: 727226
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GnomAD4 genome AF: 0.000223 AC: 34AN: 152328Hom.: 1 Cov.: 32 AF XY: 0.000242 AC XY: 18AN XY: 74484
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:3Benign:4
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:4
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Oct 26, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 01, 2025 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2025 | GFAP: BP4, BS1 - |
Alexander disease Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | New York Genome Center | Jul 10, 2020 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
.;T;.;.;.;T;.;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T;T;T;T;T;T;T
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;N;.;N;N;.;.;.;.
PrimateAI
Uncertain
T
PROVEAN
Benign
.;.;N;N;.;.;.;.;.
REVEL
Uncertain
Sift
Benign
.;.;T;T;.;.;.;.;.
Sift4G
Benign
.;.;T;T;.;T;T;.;.
Polyphen
0.0020
.;B;.;.;.;.;.;.;.
Vest4
0.12, 0.15, 0.14
MutPred
Gain of phosphorylation at T110 (P = 0.1007);Gain of phosphorylation at T110 (P = 0.1007);Gain of phosphorylation at T110 (P = 0.1007);Gain of phosphorylation at T110 (P = 0.1007);Gain of phosphorylation at T110 (P = 0.1007);Gain of phosphorylation at T110 (P = 0.1007);Gain of phosphorylation at T110 (P = 0.1007);Gain of phosphorylation at T110 (P = 0.1007);Gain of phosphorylation at T110 (P = 0.1007);
MVP
0.97
MPC
0.38
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at