rs8133778

Variant names:

• chr21-41270111-A-G
• rs8133778
• NM_012105.5:c.1304-5260A>G

Your query was ambiguous. Multiple possible variants found:

• chr21-41270111-A-G
• chr21-41270111-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012105.5(BACE2):​c.1304-5260A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.69 in 152,032 control chromosomes in the GnomAD database, including 37,016 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 0.69 (37016 hom., cov: 32)
• Consequence: BACE2 NM_012105.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.577
• Publications: 4 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.964 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BACE2	NM_012105.5	MANE Select	c.1304-5260A>G		intron	N/A	NP_036237.2
	BACE2	NM_138991.3		c.1154-5260A>G		intron	N/A	NP_620476.1
	BACE2	NM_138992.3		c.1135-5260A>G		intron	N/A	NP_620477.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BACE2	ENST00000330333.11	TSL:1 MANE Select	c.1304-5260A>G		intron	N/A	ENSP00000332979.6
	BACE2	ENST00000347667.5	TSL:1	c.1154-5260A>G		intron	N/A	ENSP00000327528.4
	BACE2	ENST00000328735.10	TSL:1	c.1135-5260A>G		intron	N/A	ENSP00000333854.6

Frequencies

GnomAD3 genomes AF: 0.690 AC: 104838 AN: 151914 Hom.: 37007 Cov.: 32

Gnomad AFR AF: 0.539

Gnomad AMI AF: 0.693

Gnomad AMR AF: 0.795

Gnomad ASJ AF: 0.738

Gnomad EAS AF: 0.987

Gnomad SAS AF: 0.837

Gnomad FIN AF: 0.677

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.723

Gnomad OTH AF: 0.733

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.690 AC: 104883 AN: 152032 Hom.: 37016 Cov.: 32 AF XY: 0.695 AC XY: 51659 AN XY: 74316

African (AFR) AF: 0.538 AC: 22294 AN: 41434

American (AMR) AF: 0.796 AC: 12171 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.738 AC: 2564 AN: 3472

East Asian (EAS) AF: 0.987 AC: 5113 AN: 5182

South Asian (SAS) AF: 0.836 AC: 4029 AN: 4820

European-Finnish (FIN) AF: 0.677 AC: 7137 AN: 10544

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.723 AC: 49167 AN: 67966

Other (OTH) AF: 0.735 AC: 1551 AN: 2110

Alfa AF: 0.719 Hom.: 116418

Bravo AF: 0.692

Asia WGS AF: 0.897 AC: 3116 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.3
DANN	Benign	0.74
PhyloP100		-0.58
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8133778; hg19: chr21-42642038;