rs734757

chr21-41171736-C-T

Variant summary

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

The NM_012105.5(BACE2):c.312+3161C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 152,148 control chromosomes in the GnomAD database, including 9,692 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 0.32 (9692 hom., cov: 33)
• Consequence: BACE2 NM_012105.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.401

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BACE2	NM_012105.5	c.312+3161C>T		intron_variant		ENST00000330333.11
BACE2	NM_138991.3	c.312+3161C>T		intron_variant
BACE2	NM_138992.3	c.312+3161C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BACE2	ENST00000330333.11	c.312+3161C>T		intron_variant		1	NM_012105.5	P1
BACE2	ENST00000328735.10	c.312+3161C>T		intron_variant		1
BACE2	ENST00000347667.5	c.312+3161C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49343 AN: 152028 Hom.: 9689 Cov.: 33

Gnomad AFR AF: 0.0890

Gnomad AMI AF: 0.372

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.355

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.440

Gnomad OTH AF: 0.341

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

GnomAD4 genome AF: 0.324 AC: 49345 AN: 152148 Hom.: 9692 Cov.: 33 AF XY: 0.322 AC XY: 23967 AN XY: 74376

Gnomad4 AFR AF: 0.0887

Gnomad4 AMR AF: 0.413

Gnomad4 ASJ AF: 0.335

Gnomad4 EAS AF: 0.355

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.373

Gnomad4 NFE AF: 0.440

Gnomad4 OTH AF: 0.337

Alfa AF: 0.414 Hom.: 19405

Bravo AF: 0.320

Asia WGS AF: 0.305 AC: 1057 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.1
Dann	Benign	0.53

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: rs734757; hg19: chr21-42543663;