rs7521

Variant names:

• chr17-46028029-A-G
• rs7521
• NM_001377265.1:c.*3858A>G

Your query was ambiguous. Multiple possible variants found:

• chr17-46028029-A-G
• chr17-46028029-A-C
• chr17-46028029-A-T

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.*3858A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 155,208 control chromosomes in the GnomAD database, including 25,269 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.57 (24752 hom., cov: 32)
  • Exomes 𝑓: 0.56 (517 hom.)
• Consequence: MAPT NM_001377265.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.448
• Publications: 65 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 17-46028029-A-G is Benign according to our data. Variant chr17-46028029-A-G is described in ClinVar as Benign. ClinVar VariationId is 323727.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.867 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.*3858A>G		3_prime_UTR	Exon 13 of 13	NP_001364194.1	A0A7I2PJZ2
	MAPT	NM_001123066.4		c.*3858A>G		3_prime_UTR	Exon 15 of 15	NP_001116538.2	P10636-9
	MAPT	NM_016835.5		c.*3858A>G		3_prime_UTR	Exon 14 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.*3858A>G		3_prime_UTR	Exon 13 of 13	ENSP00000262410.6	A0A7I2PJZ2
	MAPT	ENST00000351559.10	TSL:1	c.*3858A>G		3_prime_UTR	Exon 12 of 12	ENSP00000303214.7	P10636-8
	MAPT	ENST00000446361.7	TSL:1	c.*3858A>G		3_prime_UTR	Exon 10 of 10	ENSP00000408975.3	P10636-6

Frequencies

GnomAD3 genomes AF: 0.567 AC: 86097 AN: 151968 Hom.: 24722 Cov.: 32

Gnomad AFR AF: 0.565

Gnomad AMI AF: 0.772

Gnomad AMR AF: 0.668

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.889

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.541

Gnomad OTH AF: 0.583

GnomAD4 exome AF: 0.564 AC: 1761 AN: 3122 Hom.: 517 Cov.: 0 AF XY: 0.554 AC XY: 895 AN XY: 1616

African (AFR) AF: 0.554 AC: 31 AN: 56

American (AMR) AF: 0.500 AC: 20 AN: 40

Ashkenazi Jewish (ASJ) AF: 0.475 AC: 38 AN: 80

East Asian (EAS) AF: 0.914 AC: 329 AN: 360

South Asian (SAS) AF: 0.471 AC: 16 AN: 34

European-Finnish (FIN) AF: 0.474 AC: 180 AN: 380

Middle Eastern (MID) AF: 0.300 AC: 3 AN: 10

European-Non Finnish (NFE) AF: 0.529 AC: 1061 AN: 2004

Other (OTH) AF: 0.525 AC: 83 AN: 158

GnomAD4 genome AF: 0.567 AC: 86187 AN: 152086 Hom.: 24752 Cov.: 32 AF XY: 0.566 AC XY: 42084 AN XY: 74352

African (AFR) AF: 0.565 AC: 23429 AN: 41470

American (AMR) AF: 0.668 AC: 10214 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.520 AC: 1806 AN: 3470

East Asian (EAS) AF: 0.888 AC: 4586 AN: 5162

South Asian (SAS) AF: 0.408 AC: 1966 AN: 4824

European-Finnish (FIN) AF: 0.501 AC: 5306 AN: 10582

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.541 AC: 36759 AN: 67976

Other (OTH) AF: 0.588 AC: 1240 AN: 2110

Alfa AF: 0.437 Hom.: 27003

Bravo AF: 0.585

Asia WGS AF: 0.623 AC: 2165 AN: 3478

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	-0.75
CADD	Benign	9.2
DANN	Benign	0.60
PhyloP100		0.45
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: rs7521; hg19: chr17-44105395;