Genetic Variant BACE2:c.312+18192T>C (chr21-41186767-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_012105.5(BACE2):c.312+18192T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0398 in 152,364 control chromosomes in the GnomAD database, including 205 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 0.040 ( 205 hom., cov: 33)

Exomes 𝑓: 0.056 ( 0 hom. )

Consequence

BACE2
NM_012105.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.289

Variant links:

Genes affected

BACE2 (HGNC:934): (beta-secretase 2) This gene encodes an integral membrane glycoprotein that functions as an aspartic protease. The encoded protein cleaves amyloid precursor protein into amyloid beta peptide, which is a critical step in the etiology of Alzheimer's disease and Down syndrome. The protein precursor is further processed into an active mature peptide. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

BACE2 links:

PLAC4 (HGNC:14616): (placenta enriched 4)

PLAC4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0873 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
BACE2	NM_012105.5 link	c.312+18192T>C	intron_variant	Intron 1 of 8	ENST00000330333.11	NP_036237.2	Q9Y5Z0-1
BACE2	NM_138991.3 link	c.312+18192T>C	intron_variant	Intron 1 of 7		NP_620476.1	Q9Y5Z0-2
BACE2	NM_138992.3 link	c.312+18192T>C	intron_variant	Intron 1 of 7		NP_620477.1	Q9Y5Z0-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BACE2	ENST00000330333.11 link	c.312+18192T>C		intron_variant	Intron 1 of 8	1	NM_012105.5	ENSP00000332979.6		Q9Y5Z0-1

Frequencies

GnomAD3 genomes

AF:

0.0397

AC:

6050

AN:

152210

Hom.:

205

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0896

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.0215

Gnomad ASJ

AF:

0.0228

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0405

Gnomad FIN

AF:

0.0241

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0202

Gnomad OTH

AF:

0.0354

GnomAD4 exome

AF:

0.0556

AC:

AN:

Hom.:

Cov.:

AF XY:

0.0833

AC XY:

AN XY:

show subpopulations

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0333

GnomAD4 genome

AF:

0.0398

AC:

6062

AN:

152328

Hom.:

205

Cov.:

AF XY:

0.0401

AC XY:

2989

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0897

Gnomad4 AMR

AF:

0.0214

Gnomad4 ASJ

AF:

0.0228

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0402

Gnomad4 FIN

AF:

0.0241

Gnomad4 NFE

AF:

0.0202

Gnomad4 OTH

AF:

0.0350

Alfa

AF:

0.0239

Hom.:

Bravo

AF:

0.0406

Asia WGS

AF:

0.0210

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

6.9

DANN

Benign

0.85

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