17-45894571-C-A

Variant names:

• chr17-45894571-C-A
• rs62056779
• NM_001377265.1:c.-133C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001377265.1(MAPT):​c.-133C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 153,856 control chromosomes in the GnomAD database, including 2,154 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (2131 hom., cov: 32)
  • Exomes 𝑓: 0.13 (23 hom.)
• Consequence: MAPT NM_001377265.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.69
• Publications: 20 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-AS1 (HGNC:43738): (MAPT antisense RNA 1) Implicated in Parkinson's disease. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 17-45894571-C-A is Benign according to our data. Variant chr17-45894571-C-A is described in ClinVar as Benign. ClinVar VariationId is 323639.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.214 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.-133C>A		5_prime_UTR	Exon 1 of 13	NP_001364194.1	A0A7I2PJZ2
	MAPT	NM_001123066.4		c.-133C>A		5_prime_UTR	Exon 1 of 15	NP_001116538.2	P10636-9
	MAPT	NM_016835.5		c.-133C>A		5_prime_UTR	Exon 1 of 14	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.-133C>A		5_prime_UTR	Exon 1 of 13	ENSP00000262410.6	A0A7I2PJZ2
	MAPT	ENST00000344290.10	TSL:1	c.-133C>A		5_prime_UTR	Exon 1 of 11	ENSP00000340820.6	A0A7I2PLE3
	MAPT	ENST00000351559.10	TSL:1	c.-133C>A		5_prime_UTR	Exon 1 of 12	ENSP00000303214.7	P10636-8

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21808 AN: 152000 Hom.: 2133 Cov.: 32

Gnomad AFR AF: 0.0431

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.00155

Gnomad SAS AF: 0.0739

Gnomad FIN AF: 0.0645

Gnomad MID AF: 0.217

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.185

GnomAD4 exome AF: 0.128 AC: 223 AN: 1744 Hom.: 23 Cov.: 0 AF XY: 0.132 AC XY: 162 AN XY: 1230

African (AFR) AF: 0.00 AC: 0 AN: 30

American (AMR) AF: 0.100 AC: 1 AN: 10

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 4 AN: 14

East Asian (EAS) AF: 0.0263 AC: 1 AN: 38

South Asian (SAS) AF: 0.0638 AC: 6 AN: 94

European-Finnish (FIN) AF: 0.0877 AC: 20 AN: 228

Middle Eastern (MID) AF: 0.375 AC: 3 AN: 8

European-Non Finnish (NFE) AF: 0.144 AC: 181 AN: 1254

Other (OTH) AF: 0.103 AC: 7 AN: 68

GnomAD4 genome AF: 0.143 AC: 21798 AN: 152112 Hom.: 2131 Cov.: 32 AF XY: 0.134 AC XY: 9976 AN XY: 74376

African (AFR) AF: 0.0430 AC: 1789 AN: 41566

American (AMR) AF: 0.176 AC: 2685 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 834 AN: 3468

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5156

South Asian (SAS) AF: 0.0742 AC: 358 AN: 4826

European-Finnish (FIN) AF: 0.0645 AC: 683 AN: 10588

Middle Eastern (MID) AF: 0.212 AC: 62 AN: 292

European-Non Finnish (NFE) AF: 0.217 AC: 14742 AN: 67902

Other (OTH) AF: 0.182 AC: 384 AN: 2110

Alfa AF: 0.165 Hom.: 303

Bravo AF: 0.148

Asia WGS AF: 0.0300 AC: 105 AN: 3470

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	MAPT-Related Spectrum Disorders (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	21
DANN	Benign	0.75
PhyloP100		1.7
PromoterAI		0.056	Neutral
Mutation Taster		=300/0	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: rs62056779; hg19: chr17-43971937;