rs9891103

chr17-46014520-C-T

Variant summary

Our verdict is Benign. Variant got -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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
MAPT	NM_001377265.1	c.2173+196C>T		intron_variant		ENST00000262410.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPT	ENST00000262410.10	c.2173+196C>T		intron_variant		1	NM_001377265.1	A2

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

Gnomad4 AFR AF: 0.323

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.00155

Gnomad4 SAS AF: 0.0814

Gnomad4 FIN AF: 0.0668

Gnomad4 NFE AF: 0.223

Gnomad4 OTH AF: 0.251

Alfa AF: 0.222 Hom.: 921

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

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 03, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.9
DANN	Benign	0.57

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