17-44907331-C-T
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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 GnomAd4 at 3602 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GFAP | NM_002055.5 | c.*16G>A | 3_prime_UTR_variant | 9/9 | ENST00000588735.3 | NP_002046.1 | ||
GFAP | NM_001363846.2 | c.*16G>A | 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.*16G>A | 3_prime_UTR_variant | 9/9 | 1 | NM_002055.5 | ENSP00000466598 | 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:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
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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BayesDel_noAF
Benign
CADD
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DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at