rs11079727

Positions:

• chr17-45899447-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001377265.1(MAPT):​c.-18+4761C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 152,188 control chromosomes in the GnomAD database, including 1,817 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.13 (1817 hom., cov: 32)
• Consequence: MAPT NM_001377265.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.290

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAPT	NM_001377265.1	c.-18+4761C>A		intron_variant		ENST00000262410.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPT	ENST00000262410.10	c.-18+4761C>A		intron_variant		1	NM_001377265.1	A2

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20256 AN: 152070 Hom.: 1817 Cov.: 32

Gnomad AFR AF: 0.0316

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.114

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

GnomAD4 genome AF: 0.133 AC: 20249 AN: 152188 Hom.: 1817 Cov.: 32 AF XY: 0.137 AC XY: 10192 AN XY: 74412

Gnomad4 AFR AF: 0.0315

Gnomad4 AMR AF: 0.160

Gnomad4 ASJ AF: 0.130

Gnomad4 EAS AF: 0.00232

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.248

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.112

Alfa AF: 0.167 Hom.: 1583

Bravo AF: 0.120

Asia WGS AF: 0.0460 AC: 158 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.4
DANN	Benign	0.50

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: rs11079727; hg19: chr17-43976813;