17-45962106-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001377265.1(MAPT):c.-17-215C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 152,188 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.011 (14 hom., cov: 32)
• Consequence: MAPT NM_001377265.1 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.562

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=-0.96).
• BP6: Variant 17-45962106-C-T is Benign according to our data. Variant chr17-45962106-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1191111.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0107 (1632/152188) while in subpopulation NFE AF= 0.0152 (1033/68012). AF 95% confidence interval is 0.0144. There are 14 homozygotes in gnomad4. There are 807 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 14 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAPT	NM_001377265.1	c.-17-215C>T		intron_variant		ENST00000262410.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPT	ENST00000262410.10	c.-17-215C>T		intron_variant		1	NM_001377265.1	A2

Frequencies

GnomAD3 genomes AF: 0.0107 AC: 1632 AN: 152070 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.00316

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00334

Gnomad ASJ AF: 0.00894

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00187

Gnomad FIN AF: 0.0343

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0152

Gnomad OTH AF: 0.00621

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

GnomAD4 genome AF: 0.0107 AC: 1632 AN: 152188 Hom.: 14 Cov.: 32 AF XY: 0.0108 AC XY: 807 AN XY: 74408

Gnomad4 AFR AF: 0.00316

Gnomad4 AMR AF: 0.00333

Gnomad4 ASJ AF: 0.00894

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00187

Gnomad4 FIN AF: 0.0343

Gnomad4 NFE AF: 0.0152

Gnomad4 OTH AF: 0.00615

Alfa AF: 0.0135 Hom.: 3

Bravo AF: 0.00818

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.22
Dann	Benign	0.70

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: rs145236675; hg19: chr17-44039472;