rs878917

Variant names:

• chr17-45954019-C-T
• rs878917
• NM_001377265.1:c.-17-8302C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001377265.1(MAPT):​c.-17-8302C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0432 in 151,822 control chromosomes in the GnomAD database, including 302 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 0.043 (302 hom., cov: 32)
• Consequence: MAPT NM_001377265.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90
• Publications: 0 publications found

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]

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPT	NM_001377265.1	c.-17-8302C>T		intron_variant	Intron 1 of 12	ENST00000262410.10	NP_001364194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAPT	ENST00000262410.10	c.-17-8302C>T		intron_variant	Intron 1 of 12	1	NM_001377265.1	ENSP00000262410.6

Frequencies

GnomAD3 genomes AF: 0.0432 AC: 6549 AN: 151704 Hom.: 300 Cov.: 32

Gnomad AFR AF: 0.00828

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.0449

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.0477

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0313

Gnomad OTH AF: 0.0413

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0432 AC: 6566 AN: 151822 Hom.: 302 Cov.: 32 AF XY: 0.0483 AC XY: 3581 AN XY: 74174

African (AFR) AF: 0.00828 AC: 343 AN: 41438

American (AMR) AF: 0.102 AC: 1551 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0449 AC: 156 AN: 3472

East Asian (EAS) AF: 0.188 AC: 974 AN: 5172

South Asian (SAS) AF: 0.0484 AC: 233 AN: 4816

European-Finnish (FIN) AF: 0.103 AC: 1070 AN: 10438

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0313 AC: 2129 AN: 67914

Other (OTH) AF: 0.0427 AC: 90 AN: 2106

Alfa AF: 0.0374 Hom.: 110

Bravo AF: 0.0436

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.78
PhyloP100		-1.9
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

Other links and lift over

dbSNP: rs878917; hg19: chr17-44031385;