chr17-45961999-C-T

Position:

• chr17-45961999-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001377265.1(MAPT):​c.-17-322C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 151,904 control chromosomes in the GnomAD database, including 10,831 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.34 (10831 hom., cov: 31)
• Consequence: MAPT NM_001377265.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.70

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 17-45961999-C-T is Benign according to our data. Variant chr17-45961999-C-T is described in ClinVar as [Benign]. Clinvar id is 1259075.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.599 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAPT	NM_001377265.1	c.-17-322C>T		intron_variant		ENST00000262410.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPT	ENST00000262410.10	c.-17-322C>T		intron_variant		1	NM_001377265.1	A2

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52386 AN: 151788 Hom.: 10829 Cov.: 31

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.617

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.428

Gnomad OTH AF: 0.347

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

GnomAD4 genome AF: 0.345 AC: 52401 AN: 151904 Hom.: 10831 Cov.: 31 AF XY: 0.349 AC XY: 25943 AN XY: 74240

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.397

Gnomad4 ASJ AF: 0.459

Gnomad4 EAS AF: 0.617

Gnomad4 SAS AF: 0.496

Gnomad4 FIN AF: 0.442

Gnomad4 NFE AF: 0.428

Gnomad4 OTH AF: 0.352

Alfa AF: 0.723 Hom.: 12935

Bravo AF: 0.331

Asia WGS AF: 0.551 AC: 1912 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.28
DANN	Benign	0.37

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: rs242554; hg19: chr17-44039365;