17-44907319-G-C
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_002055.5(GFAP):c.*28C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 1,607,022 control chromosomes in the GnomAD database, including 59,675 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.26 ( 5268 hom., cov: 31)
Exomes 𝑓: 0.27 ( 54407 hom. )
Consequence
GFAP
NM_002055.5 3_prime_UTR
NM_002055.5 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.866
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 -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
Variant 17-44907319-G-C is Benign according to our data. Variant chr17-44907319-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 66424.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GFAP | NM_002055.5 | c.*28C>G | 3_prime_UTR_variant | 9/9 | ENST00000588735.3 | NP_002046.1 | ||
GFAP | NM_001363846.2 | c.*28C>G | 3_prime_UTR_variant | 10/10 | NP_001350775.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GFAP | ENST00000588735.3 | c.*28C>G | 3_prime_UTR_variant | 9/9 | 1 | NM_002055.5 | ENSP00000466598 | P1 |
Frequencies
GnomAD3 genomes AF: 0.261 AC: 39671AN: 151828Hom.: 5263 Cov.: 31
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GnomAD3 exomes AF: 0.268 AC: 67169AN: 250892Hom.: 9232 AF XY: 0.268 AC XY: 36398AN XY: 135626
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GnomAD4 exome AF: 0.272 AC: 395845AN: 1455076Hom.: 54407 Cov.: 30 AF XY: 0.273 AC XY: 197643AN XY: 724252
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GnomAD4 genome AF: 0.261 AC: 39698AN: 151946Hom.: 5268 Cov.: 31 AF XY: 0.261 AC XY: 19367AN XY: 74252
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3Other:1
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Oct 23, 2015 | - - |
not provided, no classification provided | literature only | Epithelial Biology; Institute of Medical Biology, Singapore | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | This variant is associated with the following publications: (PMID: 29746255) - |
Primary ciliary dyskinesia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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