17-45924884-A-T

Position:

• chr17-45924884-A-T

Variant summary

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

The NM_001377265.1(MAPT):​c.-18+30198A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.808 in 152,120 control chromosomes in the GnomAD database, including 49,893 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 0.81 (49893 hom., cov: 32)
• Consequence: MAPT NM_001377265.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.246

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]

LOC105371800 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAPT	NM_001377265.1	c.-18+30198A>T		intron_variant		ENST00000262410.10
LOC105371800	XR_007065818.1	n.536-406T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPT	ENST00000262410.10	c.-18+30198A>T		intron_variant		1	NM_001377265.1	A2

Frequencies

GnomAD3 genomes AF: 0.808 AC: 122880 AN: 152002 Hom.: 49847 Cov.: 32

Gnomad AFR AF: 0.847

Gnomad AMI AF: 0.832

Gnomad AMR AF: 0.870

Gnomad ASJ AF: 0.765

Gnomad EAS AF: 0.961

Gnomad SAS AF: 0.843

Gnomad FIN AF: 0.760

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.817

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

GnomAD4 genome AF: 0.808 AC: 122984 AN: 152120 Hom.: 49893 Cov.: 32 AF XY: 0.811 AC XY: 60272 AN XY: 74346

Gnomad4 AFR AF: 0.847

Gnomad4 AMR AF: 0.870

Gnomad4 ASJ AF: 0.765

Gnomad4 EAS AF: 0.961

Gnomad4 SAS AF: 0.843

Gnomad4 FIN AF: 0.760

Gnomad4 NFE AF: 0.766

Gnomad4 OTH AF: 0.819

Alfa AF: 0.779 Hom.: 6496

Bravo AF: 0.820

Asia WGS AF: 0.900 AC: 3131 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.4
DANN	Benign	0.26

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: rs242556; hg19: chr17-44002250;