rs2435214

Positions:

• chr17-45990973-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.1606-487G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 152,154 control chromosomes in the GnomAD database, including 1,824 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 0.14 (1824 hom., cov: 32)
• Consequence: MAPT NM_001377265.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.678

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAPT	NM_001377265.1	c.1606-487G>A		intron_variant		ENST00000262410.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPT	ENST00000262410.10	c.1606-487G>A		intron_variant		1	NM_001377265.1	A2

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21573 AN: 152036 Hom.: 1822 Cov.: 32

Gnomad AFR AF: 0.0602

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.0969

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.115

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

GnomAD4 genome AF: 0.142 AC: 21584 AN: 152154 Hom.: 1824 Cov.: 32 AF XY: 0.147 AC XY: 10946 AN XY: 74378

Gnomad4 AFR AF: 0.0601

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.110

Gnomad4 EAS AF: 0.202

Gnomad4 SAS AF: 0.0967

Gnomad4 FIN AF: 0.262

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.115

Alfa AF: 0.154 Hom.: 408

Bravo AF: 0.135

Asia WGS AF: 0.136 AC: 470 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.7
DANN	Benign	0.79

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: rs2435214; hg19: chr17-44068339;