rs17651213

chr17-45974558-G-A

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.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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.773

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=-0.84).
• 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_single_submitter, 1 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/exons	MANE	UniProt
MAPT	NM_001377265.1	c.220+2613G>A		intron_variant		ENST00000262410.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPT	ENST00000262410.10	c.220+2613G>A		intron_variant		1	NM_001377265.1	A2

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22020 AN: 152130 Hom.: 2145 Cov.: 32

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.: 12 AF XY: 0.170 AC XY: 79819 AN XY: 469688

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.: 32 AF XY: 0.135 AC XY: 10085 AN XY: 74436

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 11, 2018

- -

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

Other links and lift over

dbSNP: rs17651213; hg19: chr17-44051924;