Variant chr17-45894810-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001377265.1(MAPT):c.-18+124C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 152,594 control chromosomes in the GnomAD database, including 1,309 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1305 hom., cov: 32)

Exomes 𝑓: 0.14 ( 4 hom. )

Consequence

MAPT
NM_001377265.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0280

Variant links:

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]

MAPT links:

MAPT-AS1 (HGNC:43738): (MAPT antisense RNA 1) Implicated in Parkinson's disease. [provided by Alliance of Genome Resources, Apr 2022]

MAPT-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 17-45894810-C-G is Benign according to our data. Variant chr17-45894810-C-G is described in ClinVar as [Benign]. Clinvar id is 1168309.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAPT	NM_001377265.1 linkuse as main transcript	c.-18+124C>G		intron_variant		ENST00000262410.10
MAPT-AS1	NR_024559.1 linkuse as main transcript	n.34+670G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPT	ENST00000262410.10 linkuse as main transcript	c.-18+124C>G		intron_variant		1	NM_001377265.1	A2
MAPT-AS1	ENST00000634876.2 linkuse as main transcript	n.182+670G>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.124

AC:

18912

AN:

152058

Hom.:

1295

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0694

Gnomad AMI

AF:

0.0537

Gnomad AMR

AF:

0.166

Gnomad ASJ

AF:

0.158

Gnomad EAS

AF:

0.147

Gnomad SAS

AF:

0.102

Gnomad FIN

AF:

0.142

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.144

Gnomad OTH

AF:

0.151

GnomAD4 exome

AF:

0.136

AC:

AN:

418

Hom.:

Cov.:

AF XY:

0.142

AC XY:

AN XY:

310

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.250

Gnomad4 SAS exome

AF:

0.200

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.139

Gnomad4 OTH exome

AF:

0.0625

GnomAD4 genome

AF:

0.124

AC:

18939

AN:

152176

Hom.:

1305

Cov.:

AF XY:

0.124

AC XY:

9201

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.0694

Gnomad4 AMR

AF:

0.167

Gnomad4 ASJ

AF:

0.158

Gnomad4 EAS

AF:

0.148

Gnomad4 SAS

AF:

0.103

Gnomad4 FIN

AF:

0.142

Gnomad4 NFE

AF:

0.144

Gnomad4 OTH

AF:

0.149

Alfa

AF:

0.133

Hom.:

183

Bravo

AF:

0.128

Asia WGS

AF:

0.125

AC:

435

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Frontotemporal dementia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 19, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

9.4

DANN

Benign

0.62

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over