rs63751443
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001377265.1(MAPT):c.2091+29G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00338 in 1,460,154 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0020 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0035 ( 12 hom. )
Consequence
MAPT
NM_001377265.1 intron
NM_001377265.1 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.06
Genes affected
MAPT (HGNC:6893): (microtubule associated protein tau) This gene encodes the microtubule-associated protein tau (MAPT) whose transcript undergoes complex, regulated alternative splicing, giving rise to several mRNA species. MAPT transcripts are differentially expressed in the nervous system, depending on stage of neuronal maturation and neuron type. MAPT gene mutations have been associated with several neurodegenerative disorders such as Alzheimer's disease, Pick's disease, frontotemporal dementia, cortico-basal degeneration and progressive supranuclear palsy. [provided by RefSeq, Jul 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=-0.83).
BP6
?
Variant 17-46010431-G-A is Benign according to our data. Variant chr17-46010431-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 98225.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-46010431-G-A is described in Lovd as [Likely_benign]. Variant chr17-46010431-G-A is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00205 (312/152286) while in subpopulation NFE AF= 0.00334 (227/68030). AF 95% confidence interval is 0.00298. There are 1 homozygotes in gnomad4. There are 151 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome4 at 12 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAPT | NM_001377265.1 | c.2091+29G>A | intron_variant | ENST00000262410.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAPT | ENST00000262410.10 | c.2091+29G>A | intron_variant | 1 | NM_001377265.1 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00205 AC: 312AN: 152168Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.00208 AC: 338AN: 162322Hom.: 1 AF XY: 0.00205 AC XY: 175AN XY: 85504
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GnomAD4 exome AF: 0.00354 AC: 4628AN: 1307868Hom.: 12 Cov.: 20 AF XY: 0.00338 AC XY: 2199AN XY: 650458
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GnomAD4 genome ? AF: 0.00205 AC: 312AN: 152286Hom.: 1 Cov.: 32 AF XY: 0.00203 AC XY: 151AN XY: 74448
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:8Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:4Other:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 24, 2019 | This variant is associated with the following publications: (PMID: 12615641, 17071927) - |
not provided, no classification provided | literature only | VIB Department of Molecular Genetics, University of Antwerp | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2024 | MAPT: BS2 - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jul 08, 2019 | - - |
not specified Benign:1
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 04, 2021 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Frontotemporal dementia Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Aug 04, 2023 | - - |
MAPT-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 24, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
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