rs9891103

Variant names:

• chr17-46014520-C-T
• rs9891103
• NM_001377265.1:c.2173+196C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001377265.1(MAPT):​c.2173+196C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 152,060 control chromosomes in the GnomAD database, including 4,503 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.23 (4503 hom., cov: 32)
• Consequence: MAPT NM_001377265.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.274
• Publications: 17 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 17-46014520-C-T is Benign according to our data. Variant chr17-46014520-C-T is described in ClinVar as Benign. ClinVar VariationId is 1225942.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.319 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.2173+196C>T		intron	N/A	NP_001364194.1	A0A7I2PJZ2
	MAPT	NM_001123066.4		c.2002+196C>T		intron	N/A	NP_001116538.2	P10636-9
	MAPT	NM_016835.5		c.1948+196C>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.2173+196C>T		intron	N/A	ENSP00000262410.6	A0A7I2PJZ2
	MAPT	ENST00000344290.10	TSL:1	c.1882+196C>T		intron	N/A	ENSP00000340820.6	A0A7I2PLE3
	MAPT	ENST00000351559.10	TSL:1	c.997+196C>T		intron	N/A	ENSP00000303214.7	P10636-8

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34638 AN: 151942 Hom.: 4507 Cov.: 32

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0816

Gnomad FIN AF: 0.0668

Gnomad MID AF: 0.280

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.255

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

GnomAD4 genome AF: 0.228 AC: 34645 AN: 152060 Hom.: 4503 Cov.: 32 AF XY: 0.216 AC XY: 16086 AN XY: 74348

African (AFR) AF: 0.323 AC: 13395 AN: 41430

American (AMR) AF: 0.211 AC: 3225 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 870 AN: 3466

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5174

South Asian (SAS) AF: 0.0814 AC: 393 AN: 4826

European-Finnish (FIN) AF: 0.0668 AC: 708 AN: 10600

Middle Eastern (MID) AF: 0.267 AC: 78 AN: 292

European-Non Finnish (NFE) AF: 0.223 AC: 15186 AN: 67982

Other (OTH) AF: 0.251 AC: 529 AN: 2108

Alfa AF: 0.220 Hom.: 1597

Bravo AF: 0.244

Asia WGS AF: 0.0440 AC: 157 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.9
DANN	Benign	0.57
PhyloP100		0.27
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: rs9891103; hg19: chr17-44091886; COSMIC: COSV52247441;