chr21-41257148-C-T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_012105.5(BACE2):c.1135-10C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00463 in 1,614,068 control chromosomes in the GnomAD database, including 252 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.023 ( 125 hom., cov: 32)
Exomes 𝑓: 0.0027 ( 127 hom. )
Consequence
BACE2
NM_012105.5 splice_polypyrimidine_tract, intron
NM_012105.5 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.00002271
2
Clinical Significance
Conservation
PhyloP100: 0.266
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.66).
BP6
?
Variant 21-41257148-C-T is Benign according to our data. Variant chr21-41257148-C-T is described in ClinVar as [Benign]. Clinvar id is 786689.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0753 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BACE2 | NM_012105.5 | c.1135-10C>T | splice_polypyrimidine_tract_variant, intron_variant | ENST00000330333.11 | |||
BACE2 | NM_138991.3 | c.985-10C>T | splice_polypyrimidine_tract_variant, intron_variant | ||||
BACE2 | NM_138992.3 | c.1134+6247C>T | intron_variant | ||||
BACE2 | XM_017028314.2 | c.850-10C>T | splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BACE2 | ENST00000330333.11 | c.1135-10C>T | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_012105.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0229 AC: 3479AN: 152138Hom.: 122 Cov.: 32
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GnomAD3 exomes AF: 0.00660 AC: 1657AN: 251082Hom.: 62 AF XY: 0.00476 AC XY: 646AN XY: 135704
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GnomAD4 exome AF: 0.00272 AC: 3974AN: 1461812Hom.: 127 Cov.: 31 AF XY: 0.00238 AC XY: 1729AN XY: 727222
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GnomAD4 genome ? AF: 0.0230 AC: 3501AN: 152256Hom.: 125 Cov.: 32 AF XY: 0.0228 AC XY: 1695AN XY: 74448
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
BACE2-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 07, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at