dbSNP rs17651213: MAPT:c.220+2613G>A (chr17-45974558-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_001377265.1(MAPT):c.220+2613G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 1,068,254 control chromosomes in the GnomAD database, including 17,073 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 2143 hom., cov: 32)

Exomes 𝑓: 0.17 ( 14930 hom. )

Consequence

MAPT
NM_001377265.1 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.773

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:

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 17-45974558-G-A is Benign according to our data. Variant chr17-45974558-G-A is described in ClinVar as [Benign]. Clinvar id is 1222027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPT	NM_001377265.1 link	c.220+2613G>A		intron_variant	Intron 3 of 12	ENST00000262410.10	NP_001364194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAPT	ENST00000262410.10 link	c.220+2613G>A		intron_variant	Intron 3 of 12	1	NM_001377265.1	ENSP00000262410.6		A0A7I2PJZ2

Frequencies

GnomAD3 genomes

AF:

0.145

AC:

22020

AN:

152130

Hom.:

2145

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0479

Gnomad AMI

AF:

0.276

Gnomad AMR

AF:

0.176

Gnomad ASJ

AF:

0.240

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.0734

Gnomad FIN

AF:

0.0650

Gnomad MID

AF:

0.218

Gnomad NFE

AF:

0.217

Gnomad OTH

AF:

0.186

GnomAD4 exome

AF:

0.171

AC:

156937

AN:

916008

Hom.:

14930

Cov.:

AF XY:

0.170

AC XY:

79819

AN XY:

469688

show subpopulations

Gnomad4 AFR exome

AF:

0.0418

Gnomad4 AMR exome

AF:

0.130

Gnomad4 ASJ exome

AF:

0.250

Gnomad4 EAS exome

AF:

0.000741

Gnomad4 SAS exome

AF:

0.0790

Gnomad4 FIN exome

AF:

0.0706

Gnomad4 NFE exome

AF:

0.201

Gnomad4 OTH exome

AF:

0.168

GnomAD4 genome

AF:

0.145

AC:

22009

AN:

152246

Hom.:

2143

Cov.:

AF XY:

0.135

AC XY:

10085

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0478

Gnomad4 AMR

AF:

0.176

Gnomad4 ASJ

AF:

0.240

Gnomad4 EAS

AF:

0.00154

Gnomad4 SAS

AF:

0.0734

Gnomad4 FIN

AF:

0.0650

Gnomad4 NFE

AF:

0.217

Gnomad4 OTH

AF:

0.183

Alfa

AF:

0.193

Hom.:

1316

Bravo

AF:

0.150

Asia WGS

AF:

0.0310

AC:

111

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.2

DANN

Benign

0.61

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