rs12947764

Positions:

• chr17-45927076-T-G

Variant summary

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

The NM_001377265.1(MAPT):​c.-18+32390T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 151,716 control chromosomes in the GnomAD database, including 3,877 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 0.19 (3877 hom., cov: 30)
• Consequence: MAPT NM_001377265.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.282

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]

LOC105371800 (HGNC:):

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 = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAPT	NM_001377265.1	c.-18+32390T>G		intron_variant		ENST00000262410.10	NP_001364194.1
LOC105371800	XR_007065818.1	n.536-2598A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAPT	ENST00000262410.10	c.-18+32390T>G		intron_variant		1	NM_001377265.1	ENSP00000262410	A2

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29278 AN: 151596 Hom.: 3877 Cov.: 30

Gnomad AFR AF: 0.0489

Gnomad AMI AF: 0.372

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.0194

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.409

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.193 AC: 29266 AN: 151716 Hom.: 3877 Cov.: 30 AF XY: 0.197 AC XY: 14573 AN XY: 74124

Gnomad4 AFR AF: 0.0487

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.214

Gnomad4 EAS AF: 0.0193

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.409

Gnomad4 NFE AF: 0.275

Gnomad4 OTH AF: 0.165

Alfa AF: 0.216 Hom.: 479

Bravo AF: 0.168

Asia WGS AF: 0.0720 AC: 251 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	6.2
DANN	Benign	0.69

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: rs12947764; hg19: chr17-44004442;