rs4792891

Positions:

• chr17-45896132-T-G

Variant summary

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

The ENST00000262410.10(MAPT):​c.-18+1446T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 152,004 control chromosomes in the GnomAD database, including 7,196 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 0.30 (7194 hom., cov: 31)
  • Exomes 𝑓: 0.23 (2 hom.)
• Consequence: MAPT ENST00000262410.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.110

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]

MAPT-IT1 (HGNC:43741): (MAPT intronic transcript 1)

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 = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAPT	NM_001377265.1	c.-18+1446T>G		intron_variant		ENST00000262410.10	NP_001364194.1
MAPT-IT1	NR_024560.1	n.350T>G		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAPT	ENST00000262410.10	c.-18+1446T>G		intron_variant		1	NM_001377265.1	ENSP00000262410	A2
MAPT-IT1	ENST00000624111.2	n.350T>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45177 AN: 151842 Hom.: 7187 Cov.: 31

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.0173

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.310

GnomAD4 exome AF: 0.227 AC: 10 AN: 44 Hom.: 2 Cov.: 0 AF XY: 0.250 AC XY: 10 AN XY: 40

Gnomad4 AFR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.250

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.297 AC: 45208 AN: 151960 Hom.: 7194 Cov.: 31 AF XY: 0.287 AC XY: 21301 AN XY: 74268

Gnomad4 AFR AF: 0.317

Gnomad4 AMR AF: 0.262

Gnomad4 ASJ AF: 0.389

Gnomad4 EAS AF: 0.0173

Gnomad4 SAS AF: 0.131

Gnomad4 FIN AF: 0.208

Gnomad4 NFE AF: 0.335

Gnomad4 OTH AF: 0.305

Alfa AF: 0.322 Hom.: 5371

Bravo AF: 0.304

Asia WGS AF: 0.0940 AC: 330 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	7.5
DANN	Benign	0.60

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: rs4792891; hg19: chr17-43973498;