rs12149

Positions:

• chr21-41275894-C-T
• chr21-41275894-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012105.5(BACE2):​c.*270C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 445,950 control chromosomes in the GnomAD database, including 53,799 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 0.41 (14998 hom., cov: 32)
  • Exomes 𝑓: 0.50 (38801 hom.)
• Consequence: BACE2 NM_012105.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.845

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BACE2	NM_012105.5	c.*270C>T		3_prime_UTR_variant	9/9	ENST00000330333.11	NP_036237.2
BACE2	NM_138991.3	c.*270C>T		3_prime_UTR_variant	8/8		NP_620476.1
BACE2	NM_138992.3	c.*467C>T		3_prime_UTR_variant	8/8		NP_620477.1
BACE2	XM_017028314.2	c.*270C>T		3_prime_UTR_variant	10/10		XP_016883803.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BACE2	ENST00000330333.11	c.*270C>T		3_prime_UTR_variant	9/9	1	NM_012105.5	ENSP00000332979.6
BACE2	ENST00000347667.5	c.*270C>T		3_prime_UTR_variant	8/8	1		ENSP00000327528.4
BACE2	ENST00000328735.10	c.*467C>T		3_prime_UTR_variant	8/8	1		ENSP00000333854.6
BACE2	ENST00000466122.5	n.1532C>T		non_coding_transcript_exon_variant	8/8	5

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62575 AN: 151884 Hom.: 14996 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.698

Gnomad SAS AF: 0.544

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.437

GnomAD4 exome AF: 0.503 AC: 147733 AN: 293948 Hom.: 38801 Cov.: 4 AF XY: 0.507 AC XY: 76978 AN XY: 151882

Gnomad4 AFR exome AF: 0.162

Gnomad4 AMR exome AF: 0.591

Gnomad4 ASJ exome AF: 0.457

Gnomad4 EAS exome AF: 0.687

Gnomad4 SAS exome AF: 0.548

Gnomad4 FIN exome AF: 0.450

Gnomad4 NFE exome AF: 0.497

Gnomad4 OTH exome AF: 0.482

GnomAD4 genome AF: 0.412 AC: 62582 AN: 152002 Hom.: 14998 Cov.: 32 AF XY: 0.417 AC XY: 31000 AN XY: 74278

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.546

Gnomad4 ASJ AF: 0.457

Gnomad4 EAS AF: 0.697

Gnomad4 SAS AF: 0.544

Gnomad4 FIN AF: 0.448

Gnomad4 NFE AF: 0.495

Gnomad4 OTH AF: 0.439

Alfa AF: 0.484 Hom.: 31552

Bravo AF: 0.411

Asia WGS AF: 0.563 AC: 1956 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.2
DANN	Benign	0.48

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

Publications

LitVar

Other links and lift over

dbSNP: rs12149; hg19: chr21-42647821;