Variant rs638405 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_012104.6(BACE1):c.786G>C(p.Val262=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 1,612,664 control chromosomes in the GnomAD database, including 152,925 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 0.47 ( 17106 hom., cov: 31)

Exomes 𝑓: 0.42 ( 135819 hom. )

Consequence

BACE1
NM_012104.6 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0420

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP7

Synonymous conserved (PhyloP=0.042 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.643 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.786G>C	p.Val262=	synonymous_variant	5/9	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.786G>C	p.Val262=	synonymous_variant	5/9	1	NM_012104.6	ENSP00000318585	P1	P56817-1
BACE1-AS	ENST00000614401.1 linkuse as main transcript	n.282C>G		non_coding_transcript_exon_variant	4/4	4

Frequencies

GnomAD3 genomes

AF:

0.467

AC:

70950

AN:

151782

Hom.:

17088

Cov.:

show subpopulations

Gnomad AFR

AF:

0.522

Gnomad AMI

AF:

0.522

Gnomad AMR

AF:

0.564

Gnomad ASJ

AF:

0.448

Gnomad EAS

AF:

0.662

Gnomad SAS

AF:

0.615

Gnomad FIN

AF:

0.449

Gnomad MID

AF:

0.519

Gnomad NFE

AF:

0.390

Gnomad OTH

AF:

0.481

GnomAD3 exomes

AF:

0.487

AC:

122134

AN:

251006

Hom.:

31451

AF XY:

0.484

AC XY:

65607

AN XY:

135668

show subpopulations

Gnomad AFR exome

AF:

0.526

Gnomad AMR exome

AF:

0.629

Gnomad ASJ exome

AF:

0.449

Gnomad EAS exome

AF:

0.660

Gnomad SAS exome

AF:

0.599

Gnomad FIN exome

AF:

0.442

Gnomad NFE exome

AF:

0.392

Gnomad OTH exome

AF:

0.471

GnomAD4 exome

AF:

0.423

AC:

617791

AN:

1460764

Hom.:

135819

Cov.:

AF XY:

0.427

AC XY:

310616

AN XY:

726670

show subpopulations

Gnomad4 AFR exome

AF:

0.527

Gnomad4 AMR exome

AF:

0.619

Gnomad4 ASJ exome

AF:

0.445

Gnomad4 EAS exome

AF:

0.670

Gnomad4 SAS exome

AF:

0.595

Gnomad4 FIN exome

AF:

0.441

Gnomad4 NFE exome

AF:

0.386

Gnomad4 OTH exome

AF:

0.450

GnomAD4 genome

AF:

0.467

AC:

71001

AN:

151900

Hom.:

17106

Cov.:

AF XY:

0.476

AC XY:

35323

AN XY:

74218

show subpopulations

Gnomad4 AFR

AF:

0.521

Gnomad4 AMR

AF:

0.564

Gnomad4 ASJ

AF:

0.448

Gnomad4 EAS

AF:

0.662

Gnomad4 SAS

AF:

0.613

Gnomad4 FIN

AF:

0.449

Gnomad4 NFE

AF:

0.390

Gnomad4 OTH

AF:

0.483

Alfa

AF:

0.417

Hom.:

4330

Bravo

AF:

0.476

Asia WGS

AF:

0.646

AC:

2249

AN:

3478

EpiCase

AF:

0.397

EpiControl

AF:

0.406

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.65

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