chr17-45985878-C-T

Variant names:

• chr17-45985878-C-T
• rs2435211
• NM_001377265.1:c.1352-1162C>T

Variant summary

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

The NM_001377265.1(MAPT):​c.1352-1162C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 202,200 control chromosomes in the GnomAD database, including 9,111 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 (6826 hom., cov: 32)
  • Exomes 𝑓: 0.29 (2285 hom.)
• Consequence: MAPT NM_001377265.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37
• Publications: 33 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 Gene-Disease associations (from GenCC):

• late-onset Parkinson disease

  Inheritance: AD, Unknown Classification: STRONG, LIMITED Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• Pick disease

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• semantic dementia

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• supranuclear palsy, progressive, 1

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• progressive supranuclear palsy-parkinsonism syndrome

  Inheritance: AR Classification: MODERATE, LIMITED Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377265.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPT	NM_001377265.1	MANE Select	c.1352-1162C>T		intron	N/A	NP_001364194.1	A0A7I2PJZ2
	MAPT	NM_001123066.4		c.1127-1162C>T		intron	N/A	NP_001116538.2	P10636-9
	MAPT	NM_016835.5		c.1127-1162C>T		intron	N/A	NP_058519.3	P10636-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPT	ENST00000262410.10	TSL:1 MANE Select	c.1352-1162C>T		intron	N/A	ENSP00000262410.6	A0A7I2PJZ2
	MAPT	ENST00000344290.10	TSL:1	c.1352-1162C>T		intron	N/A	ENSP00000340820.6	A0A7I2PLE3
	MAPT	ENST00000351559.10	TSL:1	c.374-1162C>T		intron	N/A	ENSP00000303214.7	P10636-8

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45412 AN: 151916 Hom.: 6820 Cov.: 32

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.281

GnomAD4 exome AF: 0.294 AC: 14769 AN: 50164 Hom.: 2285 AF XY: 0.294 AC XY: 7222 AN XY: 24542

African (AFR) AF: 0.302 AC: 278 AN: 920

American (AMR) AF: 0.343 AC: 24 AN: 70

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 65 AN: 304

East Asian (EAS) AF: 0.172 AC: 34 AN: 198

South Asian (SAS) AF: 0.199 AC: 186 AN: 936

European-Finnish (FIN) AF: 0.357 AC: 5 AN: 14

Middle Eastern (MID) AF: 0.292 AC: 28 AN: 96

European-Non Finnish (NFE) AF: 0.298 AC: 13702 AN: 45976

Other (OTH) AF: 0.271 AC: 447 AN: 1650

GnomAD4 genome AF: 0.299 AC: 45446 AN: 152036 Hom.: 6826 Cov.: 32 AF XY: 0.302 AC XY: 22421 AN XY: 74320

African (AFR) AF: 0.304 AC: 12600 AN: 41444

American (AMR) AF: 0.294 AC: 4488 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 903 AN: 3468

East Asian (EAS) AF: 0.217 AC: 1122 AN: 5176

South Asian (SAS) AF: 0.185 AC: 890 AN: 4816

European-Finnish (FIN) AF: 0.387 AC: 4084 AN: 10560

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.298 AC: 20279 AN: 67984

Other (OTH) AF: 0.279 AC: 589 AN: 2108

Alfa AF: 0.293 Hom.: 7864

Bravo AF: 0.296

Asia WGS AF: 0.197 AC: 685 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.64
DANN	Benign	0.67
PhyloP100		-1.4
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: rs2435211; hg19: chr17-44063244;