chr17-45987485-C-T

Variant names:

• chr17-45987485-C-T
• rs8079215
• NM_001377265.1:c.1407+390C>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.1407+390C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.758 in 152,174 control chromosomes in the GnomAD database, including 44,030 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 0.76 (44030 hom., cov: 32)
• Consequence: MAPT NM_001377265.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.481
• Publications: 23 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377265.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPT	NM_001377265.1	MANE Select	c.1407+390C>T		intron	N/A	NP_001364194.1
	MAPT	NM_001123066.4		c.1182+390C>T		intron	N/A	NP_001116538.2
	MAPT	NM_016835.5		c.1182+390C>T		intron	N/A	NP_058519.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPT	ENST00000262410.10	TSL:1 MANE Select	c.1407+390C>T		intron	N/A	ENSP00000262410.6
	MAPT	ENST00000344290.10	TSL:1	c.1407+390C>T		intron	N/A	ENSP00000340820.6
	MAPT	ENST00000351559.10	TSL:1	c.429+390C>T		intron	N/A	ENSP00000303214.7

Frequencies

GnomAD3 genomes AF: 0.758 AC: 115273 AN: 152056 Hom.: 43987 Cov.: 32

Gnomad AFR AF: 0.821

Gnomad AMI AF: 0.849

Gnomad AMR AF: 0.800

Gnomad ASJ AF: 0.713

Gnomad EAS AF: 0.831

Gnomad SAS AF: 0.605

Gnomad FIN AF: 0.741

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.719

Gnomad OTH AF: 0.765

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

GnomAD4 genome AF: 0.758 AC: 115374 AN: 152174 Hom.: 44030 Cov.: 32 AF XY: 0.758 AC XY: 56435 AN XY: 74410

African (AFR) AF: 0.821 AC: 34074 AN: 41514

American (AMR) AF: 0.800 AC: 12236 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.713 AC: 2472 AN: 3468

East Asian (EAS) AF: 0.832 AC: 4319 AN: 5192

South Asian (SAS) AF: 0.605 AC: 2916 AN: 4818

European-Finnish (FIN) AF: 0.741 AC: 7841 AN: 10586

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.719 AC: 48886 AN: 67986

Other (OTH) AF: 0.766 AC: 1618 AN: 2112

Alfa AF: 0.725 Hom.: 72843

Bravo AF: 0.770

Asia WGS AF: 0.753 AC: 2618 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.084
DANN	Benign	0.28
PhyloP100		-0.48
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: rs8079215; hg19: chr17-44064851;