rs62063845

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The ENST00000262410.10(MAPT):​c.1732+2342T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 1,571,794 control chromosomes in the GnomAD database, including 32,173 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 2142 hom., cov: 33)
Exomes 𝑓: 0.19 ( 30031 hom. )

Consequence

MAPT
ENST00000262410.10 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7O:1

Conservation

PhyloP100: 0.732
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6
Variant 17-45993928-T-C is Benign according to our data. Variant chr17-45993928-T-C is described in ClinVar as [Benign]. Clinvar id is 98206.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-45993928-T-C is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MAPTNM_001377265.1 linkuse as main transcriptc.1732+2342T>C intron_variant ENST00000262410.10 NP_001364194.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MAPTENST00000262410.10 linkuse as main transcriptc.1732+2342T>C intron_variant 1 NM_001377265.1 ENSP00000262410 A2

Frequencies

GnomAD3 genomes
AF:
0.145
AC:
22072
AN:
152134
Hom.:
2144
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0493
Gnomad AMI
AF:
0.278
Gnomad AMR
AF:
0.176
Gnomad ASJ
AF:
0.240
Gnomad EAS
AF:
0.00154
Gnomad SAS
AF:
0.0735
Gnomad FIN
AF:
0.0649
Gnomad MID
AF:
0.220
Gnomad NFE
AF:
0.217
Gnomad OTH
AF:
0.185
GnomAD3 exomes
AF:
0.145
AC:
27044
AN:
186804
Hom.:
2576
AF XY:
0.147
AC XY:
14803
AN XY:
100560
show subpopulations
Gnomad AFR exome
AF:
0.0457
Gnomad AMR exome
AF:
0.121
Gnomad ASJ exome
AF:
0.256
Gnomad EAS exome
AF:
0.000589
Gnomad SAS exome
AF:
0.0770
Gnomad FIN exome
AF:
0.0680
Gnomad NFE exome
AF:
0.216
Gnomad OTH exome
AF:
0.182
GnomAD4 exome
AF:
0.195
AC:
276451
AN:
1419542
Hom.:
30031
Cov.:
33
AF XY:
0.192
AC XY:
135004
AN XY:
702404
show subpopulations
Gnomad4 AFR exome
AF:
0.0429
Gnomad4 AMR exome
AF:
0.128
Gnomad4 ASJ exome
AF:
0.256
Gnomad4 EAS exome
AF:
0.000879
Gnomad4 SAS exome
AF:
0.0800
Gnomad4 FIN exome
AF:
0.0720
Gnomad4 NFE exome
AF:
0.222
Gnomad4 OTH exome
AF:
0.178
GnomAD4 genome
AF:
0.145
AC:
22062
AN:
152252
Hom.:
2142
Cov.:
33
AF XY:
0.136
AC XY:
10120
AN XY:
74454
show subpopulations
Gnomad4 AFR
AF:
0.0492
Gnomad4 AMR
AF:
0.176
Gnomad4 ASJ
AF:
0.240
Gnomad4 EAS
AF:
0.00154
Gnomad4 SAS
AF:
0.0735
Gnomad4 FIN
AF:
0.0649
Gnomad4 NFE
AF:
0.217
Gnomad4 OTH
AF:
0.182
Alfa
AF:
0.195
Hom.:
1698
Bravo
AF:
0.150
Asia WGS
AF:
0.0320
AC:
112
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:7Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:4
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Benign, no assertion criteria providedclinical testingGenome Diagnostics Laboratory, University Medical Center Utrecht-- -
Benign, no assertion criteria providedclinical testingClinical Genetics, Academic Medical Center-- -
Benign, no assertion criteria providedclinical testingGenome Diagnostics Laboratory, Amsterdam University Medical Center-- -
not provided Benign:2Other:1
Benign, criteria provided, single submitterclinical testingGeneDxAug 11, 2018- -
not provided, no classification providedliterature onlyVIB Department of Molecular Genetics, University of Antwerp-- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Frontotemporal dementia Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 15, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.68
CADD
Benign
10
DANN
Benign
0.35

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.30
Details are displayed if max score is > 0.2
DS_DG_spliceai
0.30
Position offset: 49

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs62063845; hg19: chr17-44071294; API