rs1467967

chr17-45908813-G-Achr17-45908813-G-C

Variant summary

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

The NM_001377265.1(MAPT):c.-18+14127G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.661 in 152,042 control chromosomes in the GnomAD database, including 33,310 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 0.66 (33310 hom., cov: 32)
• Consequence: MAPT NM_001377265.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.594

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]

(HGNC:):

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 = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAPT	NM_001377265.1	c.-18+14127G>A		intron_variant		ENST00000262410.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPT	ENST00000262410.10	c.-18+14127G>A		intron_variant		1	NM_001377265.1	A2
	ENST00000574252.1	n.46-430C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.661 AC: 100360 AN: 151924 Hom.: 33263 Cov.: 32

Gnomad AFR AF: 0.676

Gnomad AMI AF: 0.768

Gnomad AMR AF: 0.678

Gnomad ASJ AF: 0.684

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.562

Gnomad FIN AF: 0.648

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.673

Gnomad OTH AF: 0.667

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

GnomAD4 genome AF: 0.661 AC: 100462 AN: 152042 Hom.: 33310 Cov.: 32 AF XY: 0.657 AC XY: 48828 AN XY: 74330

Gnomad4 AFR AF: 0.677

Gnomad4 AMR AF: 0.678

Gnomad4 ASJ AF: 0.684

Gnomad4 EAS AF: 0.406

Gnomad4 SAS AF: 0.563

Gnomad4 FIN AF: 0.648

Gnomad4 NFE AF: 0.673

Gnomad4 OTH AF: 0.663

Alfa AF: 0.672 Hom.: 35484

Bravo AF: 0.664

Asia WGS AF: 0.477 AC: 1663 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	0.073
Dann	Benign	0.29

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: rs1467967; hg19: chr17-43986179;