rs2435200

Positions:

• chr17-45994485-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.1733-1914G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 151,862 control chromosomes in the GnomAD database, including 12,274 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 0.40 (12274 hom., cov: 31)
• Consequence: MAPT NM_001377265.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.79

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=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAPT	NM_001377265.1	c.1733-1914G>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.1733-1914G>A		intron_variant		1	NM_001377265.1	ENSP00000262410.6

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60768 AN: 151744 Hom.: 12267 Cov.: 31

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.415

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.434

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.434

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

GnomAD4 genome AF: 0.400 AC: 60813 AN: 151862 Hom.: 12274 Cov.: 31 AF XY: 0.395 AC XY: 29284 AN XY: 74222

Gnomad4 AFR AF: 0.375

Gnomad4 AMR AF: 0.448

Gnomad4 ASJ AF: 0.434

Gnomad4 EAS AF: 0.488

Gnomad4 SAS AF: 0.305

Gnomad4 FIN AF: 0.311

Gnomad4 NFE AF: 0.416

Gnomad4 OTH AF: 0.438

Alfa AF: 0.414 Hom.: 21348

Bravo AF: 0.410

Asia WGS AF: 0.454 AC: 1579 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0060
DANN	Benign	0.68

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: rs2435200; hg19: chr17-44071851;