chr17-45981562-G-A

Position:

• chr17-45981562-G-A

Variant summary

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

The NM_001377265.1(MAPT):​c.287-1304G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 152,002 control chromosomes in the GnomAD database, including 6,785 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 0.30 (6785 hom., cov: 31)
• Consequence: MAPT NM_001377265.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.220

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAPT	NM_001377265.1	c.287-1304G>A		intron_variant		ENST00000262410.10	NP_001364194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAPT	ENST00000262410.10	c.287-1304G>A		intron_variant		1	NM_001377265.1	ENSP00000262410.6

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45078 AN: 151884 Hom.: 6782 Cov.: 31

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.406

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.296

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

GnomAD4 genome AF: 0.297 AC: 45108 AN: 152002 Hom.: 6785 Cov.: 31 AF XY: 0.300 AC XY: 22323 AN XY: 74294

Gnomad4 AFR AF: 0.266

Gnomad4 AMR AF: 0.299

Gnomad4 ASJ AF: 0.274

Gnomad4 EAS AF: 0.218

Gnomad4 SAS AF: 0.187

Gnomad4 FIN AF: 0.406

Gnomad4 NFE AF: 0.311

Gnomad4 OTH AF: 0.294

Alfa AF: 0.308 Hom.: 10514

Bravo AF: 0.292

Asia WGS AF: 0.199 AC: 692 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.63
DANN	Benign	0.78

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: rs2435207; hg19: chr17-44058928;