chr17-44907331-C-T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_002055.5(GFAP):c.*16G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0307 in 1,612,176 control chromosomes in the GnomAD database, including 880 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.024 ( 61 hom., cov: 32)
Exomes 𝑓: 0.031 ( 819 hom. )
Consequence
GFAP
NM_002055.5 3_prime_UTR
NM_002055.5 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.410
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=-0.69).
BP6
?
Variant 17-44907331-C-T is Benign according to our data. Variant chr17-44907331-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 323608.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0237 (3602/152198) while in subpopulation NFE AF= 0.0374 (2542/67988). AF 95% confidence interval is 0.0362. There are 61 homozygotes in gnomad4. There are 1726 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 3603 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GFAP | NM_002055.5 | c.*16G>A | 3_prime_UTR_variant | 9/9 | ENST00000588735.3 | ||
GFAP | NM_001363846.2 | c.*16G>A | 3_prime_UTR_variant | 10/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GFAP | ENST00000588735.3 | c.*16G>A | 3_prime_UTR_variant | 9/9 | 1 | NM_002055.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0237 AC: 3603AN: 152080Hom.: 61 Cov.: 32
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GnomAD3 exomes AF: 0.0238 AC: 5977AN: 251214Hom.: 97 AF XY: 0.0239 AC XY: 3244AN XY: 135816
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GnomAD4 exome AF: 0.0314 AC: 45879AN: 1459978Hom.: 819 Cov.: 31 AF XY: 0.0310 AC XY: 22536AN XY: 726416
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GnomAD4 genome ? AF: 0.0237 AC: 3602AN: 152198Hom.: 61 Cov.: 32 AF XY: 0.0232 AC XY: 1726AN XY: 74404
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ClinVar
Significance: Benign/Likely 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 03, 2015 | - - |
Benign, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Dec 30, 2016 | - - |
Alexander disease Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
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Name
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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