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

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]

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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPT	NM_001377265.1	c.2173+196C>T		intron_variant	Intron 11 of 12	ENST00000262410.10	NP_001364194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAPT	ENST00000262410.10	c.2173+196C>T		intron_variant	Intron 11 of 12	1	NM_001377265.1	ENSP00000262410.6

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

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 03, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

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

Publications

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Other links and lift over

dbSNP: rs9891103; hg19: chr17-44091886; COSMIC: COSV52247441;