rs2435203

chr17-46005931-T-C

Variant summary

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

The NM_001377265.1(MAPT):c.1999-4379T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,242 control chromosomes in the GnomAD database, including 2,656 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 0.16 (2656 hom., cov: 33)
• Consequence: MAPT NM_001377265.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.257

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAPT	NM_001377265.1	c.1999-4379T>C		intron_variant		ENST00000262410.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPT	ENST00000262410.10	c.1999-4379T>C		intron_variant		1	NM_001377265.1	A2

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24612 AN: 152124 Hom.: 2644 Cov.: 33

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.595

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.162 AC: 24647 AN: 152242 Hom.: 2656 Cov.: 33 AF XY: 0.170 AC XY: 12661 AN XY: 74444

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.235

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.595

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.169

Alfa AF: 0.135 Hom.: 509

Bravo AF: 0.165

Asia WGS AF: 0.394 AC: 1368 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	5.7
Dann	Benign	0.74

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: rs2435203; hg19: chr17-44083297;