rs3785883

chr17-45977067-A-G

Variant summary

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

The NM_001377265.1(MAPT):c.221-1308A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.81 in 153,306 control chromosomes in the GnomAD database, including 50,411 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 0.81 (50090 hom., cov: 34)
  • Exomes 𝑓: 0.78 (321 hom.)
• Consequence: MAPT NM_001377265.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.219

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAPT	NM_001377265.1	c.221-1308A>G		intron_variant		ENST00000262410.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPT	ENST00000262410.10	c.221-1308A>G		intron_variant		1	NM_001377265.1	A2

Frequencies

GnomAD3 genomes AF: 0.810 AC: 123294 AN: 152134 Hom.: 50057 Cov.: 34

Gnomad AFR AF: 0.819

Gnomad AMI AF: 0.773

Gnomad AMR AF: 0.814

Gnomad ASJ AF: 0.834

Gnomad EAS AF: 0.818

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.779

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.819

Gnomad OTH AF: 0.780

GnomAD4 exome AF: 0.781 AC: 823 AN: 1054 Hom.: 321 Cov.: 0 AF XY: 0.796 AC XY: 436 AN XY: 548

Gnomad4 AFR exome AF: 0.800

Gnomad4 AMR exome AF: 0.857

Gnomad4 ASJ exome AF: 0.846

Gnomad4 EAS exome AF: 0.709

Gnomad4 SAS exome AF: 0.583

Gnomad4 FIN exome AF: 0.800

Gnomad4 NFE exome AF: 0.797

Gnomad4 OTH exome AF: 0.732

GnomAD4 genome AF: 0.810 AC: 123384 AN: 152252 Hom.: 50090 Cov.: 34 AF XY: 0.806 AC XY: 60019 AN XY: 74426

Gnomad4 AFR AF: 0.818

Gnomad4 AMR AF: 0.814

Gnomad4 ASJ AF: 0.834

Gnomad4 EAS AF: 0.819

Gnomad4 SAS AF: 0.682

Gnomad4 FIN AF: 0.779

Gnomad4 NFE AF: 0.819

Gnomad4 OTH AF: 0.781

Alfa AF: 0.815 Hom.: 70636

Bravo AF: 0.816

Asia WGS AF: 0.764 AC: 2655 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	4.0
Dann	Benign	0.65

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: rs3785883; hg19: chr17-44054433;