rs1981997

chr17-45979401-G-A

Variant summary

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

The NM_001377265.1(MAPT):c.286+961G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 152,232 control chromosomes in the GnomAD database, including 2,147 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 0.14 (2145 hom., cov: 32)
  • Exomes 𝑓: 0.67 (2 hom.)
• Consequence: MAPT NM_001377265.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.244

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=-0.84).
• 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.286+961G>A		intron_variant		ENST00000262410.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPT	ENST00000262410.10	c.286+961G>A		intron_variant		1	NM_001377265.1	A2

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22022 AN: 152108 Hom.: 2147 Cov.: 32

Gnomad AFR AF: 0.0478

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0741

Gnomad FIN AF: 0.0647

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.186

GnomAD4 exome AF: 0.667 AC: 4 AN: 6 Hom.: 2 Cov.: 0 AF XY: 1.00 AC XY: 2 AN XY: 2

Gnomad4 NFE exome AF: 0.667

GnomAD4 genome AF: 0.145 AC: 22011 AN: 152226 Hom.: 2145 Cov.: 32 AF XY: 0.135 AC XY: 10085 AN XY: 74430

Gnomad4 AFR AF: 0.0477

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.240

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.0742

Gnomad4 FIN AF: 0.0647

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.183

Alfa AF: 0.195 Hom.: 1774

Bravo AF: 0.150

Asia WGS AF: 0.0310 AC: 110 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	2.8
Dann	Benign	0.74

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: rs1981997; hg19: chr17-44056767;