rs4792891

Variant names:

• chr17-45896132-T-G
• rs4792891
• NM_001377265.1:c.-18+1446T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001377265.1(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 NM_001377265.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.110
• Publications: 37 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MAPT	NM_001377265.1	c.-18+1446T>G		intron_variant	Intron 1 of 12	ENST00000262410.10	NP_001364194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAPT	ENST00000262410.10	c.-18+1446T>G		intron_variant	Intron 1 of 12	1	NM_001377265.1	ENSP00000262410.6

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

African (AFR) AF: 0.500 AC: 3 AN: 6

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.250 AC: 7 AN: 28

Other (OTH) AF: 0.00 AC: 0 AN: 2

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

African (AFR) AF: 0.317 AC: 13129 AN: 41454

American (AMR) AF: 0.262 AC: 4001 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.389 AC: 1349 AN: 3466

East Asian (EAS) AF: 0.0173 AC: 89 AN: 5132

South Asian (SAS) AF: 0.131 AC: 630 AN: 4818

European-Finnish (FIN) AF: 0.208 AC: 2194 AN: 10568

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.335 AC: 22747 AN: 67942

Other (OTH) AF: 0.305 AC: 642 AN: 2102

Alfa AF: 0.320 Hom.: 17638

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
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4792891; hg19: chr17-43973498;