chr17-45928455-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001377265.1(MAPT):​c.-18+33769C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 151,938 control chromosomes in the GnomAD database, including 21,501 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.53 ( 21501 hom., cov: 31)

Consequence

MAPT
NM_001377265.1 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.518
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 -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MAPTNM_001377265.1 linkuse as main transcriptc.-18+33769C>G intron_variant ENST00000262410.10
LOC105371800XR_007065818.1 linkuse as main transcriptn.536-3977G>C intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MAPTENST00000262410.10 linkuse as main transcriptc.-18+33769C>G intron_variant 1 NM_001377265.1 A2

Frequencies

GnomAD3 genomes
AF:
0.528
AC:
80181
AN:
151820
Hom.:
21479
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.531
Gnomad AMI
AF:
0.703
Gnomad AMR
AF:
0.467
Gnomad ASJ
AF:
0.552
Gnomad EAS
AF:
0.275
Gnomad SAS
AF:
0.469
Gnomad FIN
AF:
0.550
Gnomad MID
AF:
0.500
Gnomad NFE
AF:
0.557
Gnomad OTH
AF:
0.502
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.528
AC:
80241
AN:
151938
Hom.:
21501
Cov.:
31
AF XY:
0.525
AC XY:
38961
AN XY:
74262
show subpopulations
Gnomad4 AFR
AF:
0.532
Gnomad4 AMR
AF:
0.466
Gnomad4 ASJ
AF:
0.552
Gnomad4 EAS
AF:
0.275
Gnomad4 SAS
AF:
0.469
Gnomad4 FIN
AF:
0.550
Gnomad4 NFE
AF:
0.557
Gnomad4 OTH
AF:
0.501
Alfa
AF:
0.534
Hom.:
2717
Bravo
AF:
0.520
Asia WGS
AF:
0.355
AC:
1238
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
3.7
DANN
Benign
0.51

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

LitVar

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

Other links and lift over

dbSNP: rs1001945; hg19: chr17-44005821; API