21-41210000-T-C

Variant names:

• chr21-41210000-T-C
• rs7510366
• NM_012105.5:c.313-16266T>C

Variant summary

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

The NM_012105.5(BACE2):​c.313-16266T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.927 in 151,968 control chromosomes in the GnomAD database, including 65,851 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 0.93 (65851 hom., cov: 29)
• Consequence: BACE2 NM_012105.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• Publications: 6 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]

ENSG00000306093 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.977 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BACE2	NM_012105.5	MANE Select	c.313-16266T>C		intron	N/A	NP_036237.2
	BACE2	NM_138991.3		c.313-16266T>C		intron	N/A	NP_620476.1	Q9Y5Z0-2
	BACE2	NM_138992.3		c.313-16266T>C		intron	N/A	NP_620477.1	Q9Y5Z0-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BACE2	ENST00000330333.11	TSL:1 MANE Select	c.313-16266T>C		intron	N/A	ENSP00000332979.6	Q9Y5Z0-1
	BACE2	ENST00000347667.5	TSL:1	c.313-16266T>C		intron	N/A	ENSP00000327528.4	Q9Y5Z0-2
	BACE2	ENST00000328735.10	TSL:1	c.313-16266T>C		intron	N/A	ENSP00000333854.6	Q9Y5Z0-3

Frequencies

GnomAD3 genomes AF: 0.928 AC: 140842 AN: 151850 Hom.: 65800 Cov.: 29

Gnomad AFR AF: 0.985

Gnomad AMI AF: 0.976

Gnomad AMR AF: 0.753

Gnomad ASJ AF: 0.948

Gnomad EAS AF: 0.800

Gnomad SAS AF: 0.956

Gnomad FIN AF: 0.873

Gnomad MID AF: 0.959

Gnomad NFE AF: 0.946

Gnomad OTH AF: 0.926

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

GnomAD4 genome AF: 0.927 AC: 140946 AN: 151968 Hom.: 65851 Cov.: 29 AF XY: 0.921 AC XY: 68375 AN XY: 74262

African (AFR) AF: 0.985 AC: 40835 AN: 41450

American (AMR) AF: 0.753 AC: 11482 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.948 AC: 3290 AN: 3470

East Asian (EAS) AF: 0.801 AC: 4120 AN: 5144

South Asian (SAS) AF: 0.956 AC: 4586 AN: 4796

European-Finnish (FIN) AF: 0.873 AC: 9219 AN: 10566

Middle Eastern (MID) AF: 0.956 AC: 281 AN: 294

European-Non Finnish (NFE) AF: 0.946 AC: 64301 AN: 67970

Other (OTH) AF: 0.920 AC: 1942 AN: 2112

Alfa AF: 0.933 Hom.: 117441

Bravo AF: 0.915

Asia WGS AF: 0.865 AC: 3010 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.20
DANN	Benign	0.43
PhyloP100		-1.3
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: rs7510366; hg19: chr21-42581927;