rs734757

Variant names:

• chr21-41171736-C-T
• rs734757
• NM_012105.5:c.312+3161C>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+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
• 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]

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.436 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+3161C>T		intron	N/A	NP_036237.2
	BACE2	NM_138991.3		c.312+3161C>T		intron	N/A	NP_620476.1	Q9Y5Z0-2
	BACE2	NM_138992.3		c.312+3161C>T		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+3161C>T		intron	N/A	ENSP00000332979.6	Q9Y5Z0-1
	BACE2	ENST00000347667.5	TSL:1	c.312+3161C>T		intron	N/A	ENSP00000327528.4	Q9Y5Z0-2
	BACE2	ENST00000328735.10	TSL:1	c.312+3161C>T		intron	N/A	ENSP00000333854.6	Q9Y5Z0-3

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

African (AFR) AF: 0.0887 AC: 3684 AN: 41512

American (AMR) AF: 0.413 AC: 6321 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 1163 AN: 3470

East Asian (EAS) AF: 0.355 AC: 1839 AN: 5180

South Asian (SAS) AF: 0.278 AC: 1340 AN: 4818

European-Finnish (FIN) AF: 0.373 AC: 3940 AN: 10572

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.440 AC: 29910 AN: 67986

Other (OTH) AF: 0.337 AC: 711 AN: 2112

Alfa AF: 0.407 Hom.: 28297

Bravo AF: 0.320

Asia WGS AF: 0.305 AC: 1057 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.1
DANN	Benign	0.53
PhyloP100		-0.40
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: rs734757; hg19: chr21-42543663;