17-46006582-T-C

Position:

• chr17-46006582-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001377265.1(MAPT):​c.1999-3728T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 151,692 control chromosomes in the GnomAD database, including 8,135 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 0.31 (8135 hom., cov: 32)
• Consequence: MAPT NM_001377265.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.118

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAPT	NM_001377265.1	c.1999-3728T>C		intron_variant		ENST00000262410.10	NP_001364194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAPT	ENST00000262410.10	c.1999-3728T>C		intron_variant		1	NM_001377265.1	ENSP00000262410.6

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47031 AN: 151574 Hom.: 8128 Cov.: 32

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.480

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.369

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

GnomAD4 genome AF: 0.310 AC: 47050 AN: 151692 Hom.: 8135 Cov.: 32 AF XY: 0.306 AC XY: 22707 AN XY: 74148

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.377

Gnomad4 ASJ AF: 0.391

Gnomad4 EAS AF: 0.479

Gnomad4 SAS AF: 0.288

Gnomad4 FIN AF: 0.249

Gnomad4 NFE AF: 0.385

Gnomad4 OTH AF: 0.375

Alfa AF: 0.298 Hom.: 1968

Bravo AF: 0.310

Asia WGS AF: 0.391 AC: 1361 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.6
DANN	Benign	0.34

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

Other links and lift over

dbSNP: rs8067056; hg19: chr17-44083948;