Genetic Variant BACE2:c.312+7392A>G (chr21-41175967-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_012105.5(BACE2):c.312+7392A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 152,008 control chromosomes in the GnomAD database, including 5,666 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 0.27 ( 5666 hom., cov: 32)

Exomes 𝑓: 0.083 ( 0 hom. )

Consequence

BACE2
NM_012105.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.407

Publications

11 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012105.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BACE2	NM_012105.5	MANE Select	c.312+7392A>G	intron	N/A	NP_036237.2
BACE2	NM_138991.3		c.312+7392A>G	intron	N/A	NP_620476.1	Q9Y5Z0-2
BACE2	NM_138992.3		c.312+7392A>G	intron	N/A	NP_620477.1	Q9Y5Z0-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BACE2	ENST00000330333.11	TSL:1 MANE Select	c.312+7392A>G	intron	N/A	ENSP00000332979.6	Q9Y5Z0-1
BACE2	ENST00000347667.5	TSL:1	c.312+7392A>G	intron	N/A	ENSP00000327528.4	Q9Y5Z0-2
BACE2	ENST00000328735.10	TSL:1	c.312+7392A>G	intron	N/A	ENSP00000333854.6	Q9Y5Z0-3

Frequencies

GnomAD3 genomes

AF:

0.269

AC:

40791

AN:

151878

Hom.:

5658

Cov.:

show subpopulations

Gnomad AFR

AF:

0.255

Gnomad AMI

AF:

0.263

Gnomad AMR

AF:

0.286

Gnomad ASJ

AF:

0.374

Gnomad EAS

AF:

0.190

Gnomad SAS

AF:

0.328

Gnomad FIN

AF:

0.231

Gnomad MID

AF:

0.453

Gnomad NFE

AF:

0.274

Gnomad OTH

AF:

0.288

GnomAD4 exome

AF:

0.0833

AC:

AN:

Hom.:

Cov.:

AF XY:

0.100

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.269

AC:

40849

AN:

151996

Hom.:

5666

Cov.:

AF XY:

0.271

AC XY:

20130

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.255

AC:

10564

AN:

41430

American (AMR)

AF:

0.286

AC:

4371

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.374

AC:

1298

AN:

3466

East Asian (EAS)

AF:

0.190

AC:

981

AN:

5160

South Asian (SAS)

AF:

0.328

AC:

1577

AN:

4806

European-Finnish (FIN)

AF:

0.231

AC:

2441

AN:

10570

Middle Eastern (MID)

AF:

0.463

AC:

136

AN:

294

European-Non Finnish (NFE)

AF:

0.274

AC:

18636

AN:

67976

Other (OTH)

AF:

0.288

AC:

606

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1515

3031

4546

6062

7577

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

430

860

1290

1720

2150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.277

Hom.:

10141

Bravo

AF:

0.271

Asia WGS

AF:

0.267

AC:

926

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.35

(source)

DANN

Benign

0.48

PhyloP100

-0.41

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over