Variant 11-117289162-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_012104.6(BACE1):c.*404T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 197,860 control chromosomes in the GnomAD database, including 1,428 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.12 ( 1110 hom., cov: 32)

Exomes 𝑓: 0.11 ( 318 hom. )

Consequence

BACE1
NM_012104.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.34

Variant links:

Genes affected

BACE1 (HGNC:933): (beta-secretase 1) This gene encodes a member of the peptidase A1 family of aspartic proteases. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the mature protease. This transmembrane protease catalyzes the first step in the formation of amyloid beta peptide from amyloid precursor protein. Amyloid beta peptides are the main constituent of amyloid beta plaques, which accumulate in the brains of human Alzheimer's disease patients. [provided by RefSeq, Nov 2015]

BACE1 links:

BACE1-AS (HGNC:37125): (BACE1 antisense RNA) This gene encodes an unspliced long non-coding RNA transcribed from the opposite strand to BACE1. The encoded transcript is thought to form an RNA duplex with BACE1 mRNA thereby regulating its expression and is also thought to promote post-transcriptional feed-forward regulation of BACE1. This may lead to increased levels of beta amyloid and increased senile plaque deposition, and therefore may play a role in the pathophysiology of Alzheimer's disease. [provided by RefSeq, Jan 2015]

BACE1-AS links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BACE1	NM_012104.6 linkuse as main transcript	c.*404T>A		3_prime_UTR_variant	9/9	ENST00000313005.11	NP_036236.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BACE1	ENST00000313005.11 linkuse as main transcript	c.*404T>A		3_prime_UTR_variant	9/9	1	NM_012104.6	ENSP00000318585	P1	P56817-1

Frequencies

GnomAD3 genomes

AF:

0.122

AC:

18506

AN:

152060

Hom.:

1106

Cov.:

show subpopulations

Gnomad AFR

AF:

0.122

Gnomad AMI

AF:

0.0987

Gnomad AMR

AF:

0.115

Gnomad ASJ

AF:

0.163

Gnomad EAS

AF:

0.0869

Gnomad SAS

AF:

0.110

Gnomad FIN

AF:

0.145

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.121

Gnomad OTH

AF:

0.114

GnomAD4 exome

AF:

0.109

AC:

4966

AN:

45682

Hom.:

318

Cov.:

AF XY:

0.109

AC XY:

2556

AN XY:

23478

show subpopulations

Gnomad4 AFR exome

AF:

0.118

Gnomad4 AMR exome

AF:

0.123

Gnomad4 ASJ exome

AF:

0.152

Gnomad4 EAS exome

AF:

0.0908

Gnomad4 SAS exome

AF:

0.106

Gnomad4 FIN exome

AF:

0.129

Gnomad4 NFE exome

AF:

0.105

Gnomad4 OTH exome

AF:

0.109

GnomAD4 genome

AF:

0.122

AC:

18520

AN:

152178

Hom.:

1110

Cov.:

AF XY:

0.122

AC XY:

9085

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.122

Gnomad4 AMR

AF:

0.115

Gnomad4 ASJ

AF:

0.163

Gnomad4 EAS

AF:

0.0869

Gnomad4 SAS

AF:

0.111

Gnomad4 FIN

AF:

0.145

Gnomad4 NFE

AF:

0.121

Gnomad4 OTH

AF:

0.116

Alfa

AF:

0.121

Hom.:

147

Bravo

AF:

0.121

Asia WGS

AF:

0.0890

AC:

308

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.80

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over