rs8130833

Variant names:

• chr21-41184958-A-G
• rs8130833
• NM_012105.5:c.312+16383A>G

Your query was ambiguous. Multiple possible variants found:

• chr21-41184958-A-G
• chr21-41184958-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.312+16383A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 166,910 control chromosomes in the GnomAD database, including 12,584 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 0.37 (11993 hom., cov: 33)
  • Exomes 𝑓: 0.28 (591 hom.)
• Consequence: BACE2 NM_012105.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.78
• Publications: 17 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]

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.595 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.312+16383A>G		intron	N/A	NP_036237.2
	BACE2	NM_138991.3		c.312+16383A>G		intron	N/A	NP_620476.1	Q9Y5Z0-2
	BACE2	NM_138992.3		c.312+16383A>G		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.312+16383A>G		intron	N/A	ENSP00000332979.6	Q9Y5Z0-1
	BACE2	ENST00000347667.5	TSL:1	c.312+16383A>G		intron	N/A	ENSP00000327528.4	Q9Y5Z0-2
	BACE2	ENST00000328735.10	TSL:1	c.312+16383A>G		intron	N/A	ENSP00000333854.6	Q9Y5Z0-3

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55832 AN: 151966 Hom.: 11937 Cov.: 33

Gnomad AFR AF: 0.600

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.280

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.371

GnomAD4 exome AF: 0.283 AC: 4197 AN: 14826 Hom.: 591 Cov.: 0 AF XY: 0.282 AC XY: 1988 AN XY: 7044

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AF: 1.00 AC: 4 AN: 4

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.250 AC: 1 AN: 4

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.283 AC: 4143 AN: 14638

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.238 AC: 20 AN: 84

Other (OTH) AF: 0.322 AC: 29 AN: 90

GnomAD4 genome AF: 0.368 AC: 55951 AN: 152084 Hom.: 11993 Cov.: 33 AF XY: 0.362 AC XY: 26943 AN XY: 74344

African (AFR) AF: 0.601 AC: 24910 AN: 41446

American (AMR) AF: 0.321 AC: 4900 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 876 AN: 3468

East Asian (EAS) AF: 0.154 AC: 795 AN: 5174

South Asian (SAS) AF: 0.259 AC: 1248 AN: 4816

European-Finnish (FIN) AF: 0.280 AC: 2959 AN: 10586

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.281 AC: 19103 AN: 67988

Other (OTH) AF: 0.374 AC: 790 AN: 2114

Alfa AF: 0.303 Hom.: 7998

Bravo AF: 0.381

Asia WGS AF: 0.233 AC: 812 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.072
DANN	Benign	0.24
PhyloP100		-2.8
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: rs8130833; hg19: chr21-42556885;