chr17-45894810-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001377265.1(MAPT):​c.-18+124C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 152,594 control chromosomes in the GnomAD database, including 1,309 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1305 hom., cov: 32)
Exomes 𝑓: 0.14 ( 4 hom. )

Consequence

MAPT
NM_001377265.1 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0280

Publications

6 publications found
Variant links:
Genes affected
MAPT-AS1 (HGNC:43738): (MAPT antisense RNA 1) Implicated in Parkinson's disease. [provided by Alliance of Genome Resources, Apr 2022]
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]
MAPT Gene-Disease associations (from GenCC):
  • Pick disease
    Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
  • semantic dementia
    Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
  • supranuclear palsy, progressive, 1
    Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
  • late-onset Parkinson disease
    Inheritance: Unknown, AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
  • progressive supranuclear palsy-parkinsonism syndrome
    Inheritance: AR Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant 17-45894810-C-G is Benign according to our data. Variant chr17-45894810-C-G is described in ClinVar as [Benign]. Clinvar id is 1168309.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAPTNM_001377265.1 linkc.-18+124C>G intron_variant Intron 1 of 12 ENST00000262410.10 NP_001364194.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MAPTENST00000262410.10 linkc.-18+124C>G intron_variant Intron 1 of 12 1 NM_001377265.1 ENSP00000262410.6 A0A7I2PJZ2

Frequencies

GnomAD3 genomes
AF:
0.124
AC:
18912
AN:
152058
Hom.:
1295
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0694
Gnomad AMI
AF:
0.0537
Gnomad AMR
AF:
0.166
Gnomad ASJ
AF:
0.158
Gnomad EAS
AF:
0.147
Gnomad SAS
AF:
0.102
Gnomad FIN
AF:
0.142
Gnomad MID
AF:
0.228
Gnomad NFE
AF:
0.144
Gnomad OTH
AF:
0.151
GnomAD4 exome
AF:
0.136
AC:
57
AN:
418
Hom.:
4
Cov.:
0
AF XY:
0.142
AC XY:
44
AN XY:
310
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
6
American (AMR)
AC:
0
AN:
0
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
2
East Asian (EAS)
AF:
0.250
AC:
1
AN:
4
South Asian (SAS)
AF:
0.200
AC:
2
AN:
10
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
6
Middle Eastern (MID)
AF:
0.250
AC:
2
AN:
8
European-Non Finnish (NFE)
AF:
0.139
AC:
51
AN:
366
Other (OTH)
AF:
0.0625
AC:
1
AN:
16
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.498
Heterozygous variant carriers
0
3
7
10
14
17
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.124
AC:
18939
AN:
152176
Hom.:
1305
Cov.:
32
AF XY:
0.124
AC XY:
9201
AN XY:
74400
show subpopulations
African (AFR)
AF:
0.0694
AC:
2883
AN:
41558
American (AMR)
AF:
0.167
AC:
2550
AN:
15298
Ashkenazi Jewish (ASJ)
AF:
0.158
AC:
548
AN:
3472
East Asian (EAS)
AF:
0.148
AC:
757
AN:
5128
South Asian (SAS)
AF:
0.103
AC:
497
AN:
4824
European-Finnish (FIN)
AF:
0.142
AC:
1506
AN:
10610
Middle Eastern (MID)
AF:
0.245
AC:
72
AN:
294
European-Non Finnish (NFE)
AF:
0.144
AC:
9762
AN:
67966
Other (OTH)
AF:
0.149
AC:
315
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.506
Heterozygous variant carriers
0
857
1714
2571
3428
4285
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
214
428
642
856
1070
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.133
Hom.:
183
Bravo
AF:
0.128
Asia WGS
AF:
0.125
AC:
435
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Frontotemporal dementia Benign:1
Jan 06, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

not provided Benign:1
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
9.4
DANN
Benign
0.62
PhyloP100
0.028
PromoterAI
-0.022
Neutral
Mutation Taster
=100/0
polymorphism (auto)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs3744456; hg19: chr17-43972176; API