dbSNP rs2252576: BACE2:c.748-10C>T (chr21-41243366-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_012105.5(BACE2):c.748-10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 1,578,428 control chromosomes in the GnomAD database, including 61,160 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.36 ( 13983 hom., cov: 32)

Exomes 𝑓: 0.24 ( 47177 hom. )

Consequence

BACE2
NM_012105.5 intron

Scores

Splicing: ADA: 0.00001374

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.359

Publications

24 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:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_012105.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 21-41243366-C-T is Benign according to our data. Variant chr21-41243366-C-T is described in ClinVar as Benign. ClinVar VariationId is 3059580.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.715 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.748-10C>T	intron	N/A	NP_036237.2
BACE2	NM_138991.3		c.748-10C>T	intron	N/A	NP_620476.1	Q9Y5Z0-2
BACE2	NM_138992.3		c.748-10C>T	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.748-10C>T	intron	N/A	ENSP00000332979.6	Q9Y5Z0-1
BACE2	ENST00000347667.5	TSL:1	c.748-10C>T	intron	N/A	ENSP00000327528.4	Q9Y5Z0-2
BACE2	ENST00000328735.10	TSL:1	c.748-10C>T	intron	N/A	ENSP00000333854.6	Q9Y5Z0-3

Frequencies

GnomAD3 genomes

AF:

0.363

AC:

55071

AN:

151858

Hom.:

13951

Cov.:

show subpopulations

Gnomad AFR

AF:

0.722

Gnomad AMI

AF:

0.221

Gnomad AMR

AF:

0.254

Gnomad ASJ

AF:

0.277

Gnomad EAS

AF:

0.0720

Gnomad SAS

AF:

0.192

Gnomad FIN

AF:

0.190

Gnomad MID

AF:

0.212

Gnomad NFE

AF:

0.237

Gnomad OTH

AF:

0.338

GnomAD2 exomes

AF:

0.235

AC:

54424

AN:

231610

AF XY:

0.228

show subpopulations

Gnomad AFR exome

AF:

0.731

Gnomad AMR exome

AF:

0.142

Gnomad ASJ exome

AF:

0.273

Gnomad EAS exome

AF:

0.0602

Gnomad FIN exome

AF:

0.196

Gnomad NFE exome

AF:

0.236

Gnomad OTH exome

AF:

0.228

GnomAD4 exome

AF:

0.241

AC:

343972

AN:

1426452

Hom.:

47177

Cov.:

AF XY:

0.238

AC XY:

168736

AN XY:

707658

show subpopulations

African (AFR)

AF:

0.743

AC:

23830

AN:

32062

American (AMR)

AF:

0.155

AC:

6238

AN:

40300

Ashkenazi Jewish (ASJ)

AF:

0.279

AC:

6985

AN:

25058

East Asian (EAS)

AF:

0.0712

AC:

2774

AN:

38934

South Asian (SAS)

AF:

0.183

AC:

14403

AN:

78764

European-Finnish (FIN)

AF:

0.197

AC:

10429

AN:

52876

Middle Eastern (MID)

AF:

0.240

AC:

1353

AN:

5640

European-Non Finnish (NFE)

AF:

0.240

AC:

262809

AN:

1093886

Other (OTH)

AF:

0.257

AC:

15151

AN:

58932

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

10574

21147

31721

42294

52868

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9150

18300

27450

36600

45750

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.363

AC:

55148

AN:

151976

Hom.:

13983

Cov.:

AF XY:

0.354

AC XY:

26273

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.722

AC:

29919

AN:

41428

American (AMR)

AF:

0.254

AC:

3877

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.277

AC:

961

AN:

3472

East Asian (EAS)

AF:

0.0720

AC:

372

AN:

5170

South Asian (SAS)

AF:

0.193

AC:

928

AN:

4816

European-Finnish (FIN)

AF:

0.190

AC:

2007

AN:

10560

Middle Eastern (MID)

AF:

0.214

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.237

AC:

16108

AN:

67952

Other (OTH)

AF:

0.338

AC:

712

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1404

2808

4211

5615

7019

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

468

936

1404

1872

2340

<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:

0.280

Hom.:

13789

Bravo

AF:

0.381

Asia WGS

AF:

0.173

AC:

604

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

BACE2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

3.9

(source)

DANN

Benign

0.44

PhyloP100

0.36

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000014

dbscSNV1_RF

Benign

0.0

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over