rs17651507

Variant names:

• chr17-45981644-A-T
• rs17651507
• NM_001377265.1:c.287-1222A>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.287-1222A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 152,116 control chromosomes in the GnomAD database, including 3,992 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 0.20 (3992 hom., cov: 30)
• Consequence: MAPT NM_001377265.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.695
• Publications: 20 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPT	NM_001377265.1	c.287-1222A>T		intron_variant	Intron 4 of 12	ENST00000262410.10	NP_001364194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAPT	ENST00000262410.10	c.287-1222A>T		intron_variant	Intron 4 of 12	1	NM_001377265.1	ENSP00000262410.6

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30906 AN: 151998 Hom.: 3996 Cov.: 30

Gnomad AFR AF: 0.0508

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.197

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

GnomAD4 genome AF: 0.203 AC: 30899 AN: 152116 Hom.: 3992 Cov.: 30 AF XY: 0.205 AC XY: 15219 AN XY: 74344

African (AFR) AF: 0.0506 AC: 2102 AN: 41518

American (AMR) AF: 0.174 AC: 2665 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 999 AN: 3468

East Asian (EAS) AF: 0.170 AC: 881 AN: 5172

South Asian (SAS) AF: 0.397 AC: 1909 AN: 4808

European-Finnish (FIN) AF: 0.282 AC: 2979 AN: 10578

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.276 AC: 18782 AN: 67982

Other (OTH) AF: 0.195 AC: 412 AN: 2110

Alfa AF: 0.258 Hom.: 3077

Bravo AF: 0.183

Asia WGS AF: 0.242 AC: 845 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.76
PhyloP100		-0.69
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: rs17651507; hg19: chr17-44059010;