rs17651507

chr17-45981644-A-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
MAPT	NM_001377265.1	c.287-1222A>T		intron_variant		ENST00000262410.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPT	ENST00000262410.10	c.287-1222A>T		intron_variant		1	NM_001377265.1	A2

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

Gnomad4 AFR AF: 0.0506

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.288

Gnomad4 EAS AF: 0.170

Gnomad4 SAS AF: 0.397

Gnomad4 FIN AF: 0.282

Gnomad4 NFE AF: 0.276

Gnomad4 OTH AF: 0.195

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

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: rs17651507; hg19: chr17-44059010;