rs2471738

chr17-45998697-C-T

Variant summary

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

The NM_001377265.1(MAPT):c.1998+2033C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,060 control chromosomes in the GnomAD database, including 2,897 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 0.19 (2897 hom., cov: 31)
• Consequence: MAPT NM_001377265.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.228

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAPT	NM_001377265.1	c.1998+2033C>T		intron_variant		ENST00000262410.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPT	ENST00000262410.10	c.1998+2033C>T		intron_variant		1	NM_001377265.1	A2

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28317 AN: 151942 Hom.: 2894 Cov.: 31

Gnomad AFR AF: 0.0984

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.175

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

GnomAD4 genome AF: 0.186 AC: 28336 AN: 152060 Hom.: 2897 Cov.: 31 AF XY: 0.191 AC XY: 14167 AN XY: 74340

Gnomad4 AFR AF: 0.0984

Gnomad4 AMR AF: 0.224

Gnomad4 ASJ AF: 0.151

Gnomad4 EAS AF: 0.204

Gnomad4 SAS AF: 0.139

Gnomad4 FIN AF: 0.285

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.174

Alfa AF: 0.212 Hom.: 2083

Bravo AF: 0.181

Asia WGS AF: 0.165 AC: 570 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.40
Dann	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2471738; hg19: chr17-44076063;