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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BACE2	NM_012105.5	c.312+16383A>G		intron_variant	Intron 1 of 8	ENST00000330333.11	NP_036237.2
PLAC4	NR_148920.1	n.282T>C		non_coding_transcript_exon_variant	Exon 1 of 1
BACE2	NM_138991.3	c.312+16383A>G		intron_variant	Intron 1 of 7		NP_620476.1
BACE2	NM_138992.3	c.312+16383A>G		intron_variant	Intron 1 of 7		NP_620477.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BACE2	ENST00000330333.11	c.312+16383A>G		intron_variant	Intron 1 of 8	1	NM_012105.5	ENSP00000332979.6

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 v4.3

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;