17-45985878-C-T

Position:

• chr17-45985878-C-T

Variant summary

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

The ENST00000262410.10(MAPT):​c.1352-1162C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 202,200 control chromosomes in the GnomAD database, including 9,111 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 (6826 hom., cov: 32)
  • Exomes 𝑓: 0.29 (2285 hom.)
• Consequence: MAPT ENST00000262410.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAPT	NM_001377265.1	c.1352-1162C>T		intron_variant		ENST00000262410.10	NP_001364194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAPT	ENST00000262410.10	c.1352-1162C>T		intron_variant		1	NM_001377265.1	ENSP00000262410	A2

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45412 AN: 151916 Hom.: 6820 Cov.: 32

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.281

GnomAD4 exome AF: 0.294 AC: 14769 AN: 50164 Hom.: 2285 AF XY: 0.294 AC XY: 7222 AN XY: 24542

Gnomad4 AFR exome AF: 0.302

Gnomad4 AMR exome AF: 0.343

Gnomad4 ASJ exome AF: 0.214

Gnomad4 EAS exome AF: 0.172

Gnomad4 SAS exome AF: 0.199

Gnomad4 FIN exome AF: 0.357

Gnomad4 NFE exome AF: 0.298

Gnomad4 OTH exome AF: 0.271

GnomAD4 genome AF: 0.299 AC: 45446 AN: 152036 Hom.: 6826 Cov.: 32 AF XY: 0.302 AC XY: 22421 AN XY: 74320

Gnomad4 AFR AF: 0.304

Gnomad4 AMR AF: 0.294

Gnomad4 ASJ AF: 0.260

Gnomad4 EAS AF: 0.217

Gnomad4 SAS AF: 0.185

Gnomad4 FIN AF: 0.387

Gnomad4 NFE AF: 0.298

Gnomad4 OTH AF: 0.279

Alfa AF: 0.294 Hom.: 5105

Bravo AF: 0.296

Asia WGS AF: 0.197 AC: 685 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.64
DANN	Benign	0.67

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: rs2435211; hg19: chr17-44063244;