chr21-41205599-C-T

Variant names:

• chr21-41205599-C-T
• rs10483074
• NM_012105.5:c.313-20667C>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.313-20667C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 152,202 control chromosomes in the GnomAD database, including 3,841 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 0.12 (3841 hom., cov: 33)
• Consequence: BACE2 NM_012105.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.815
• Publications: 1 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]

ENSG00000306093 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BACE2	NM_012105.5	c.313-20667C>T		intron_variant	Intron 1 of 8	ENST00000330333.11	NP_036237.2
BACE2	NM_138991.3	c.313-20667C>T		intron_variant	Intron 1 of 7		NP_620476.1
BACE2	NM_138992.3	c.313-20667C>T		intron_variant	Intron 1 of 7		NP_620477.1
BACE2	XM_017028314.2	c.-483-4924C>T		intron_variant	Intron 1 of 9		XP_016883803.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BACE2	ENST00000330333.11	c.313-20667C>T		intron_variant	Intron 1 of 8	1	NM_012105.5	ENSP00000332979.6

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18872 AN: 152084 Hom.: 3822 Cov.: 33

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0524

Gnomad ASJ AF: 0.00950

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.00284

Gnomad OTH AF: 0.0967

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

GnomAD4 genome AF: 0.124 AC: 18949 AN: 152202 Hom.: 3841 Cov.: 33 AF XY: 0.120 AC XY: 8906 AN XY: 74448

African (AFR) AF: 0.427 AC: 17687 AN: 41458

American (AMR) AF: 0.0524 AC: 802 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00950 AC: 33 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00187 AC: 9 AN: 4822

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10622

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.00282 AC: 192 AN: 68016

Other (OTH) AF: 0.0981 AC: 207 AN: 2110

Alfa AF: 0.0697 Hom.: 483

Bravo AF: 0.142

Asia WGS AF: 0.0350 AC: 121 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.70
DANN	Benign	0.53
PhyloP100		-0.81
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: rs10483074; hg19: chr21-42577526;