chr12-89697090-A-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001366521.1(ATP2B1):​c.-222+11506T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 148,298 control chromosomes in the GnomAD database, including 2,077 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 0.15 ( 2077 hom., cov: 29)

Consequence

ATP2B1
NM_001366521.1 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.108

Publications

12 publications found
Variant links:
Genes affected
ATP2B1 (HGNC:814): (ATPase plasma membrane Ca2+ transporting 1) The protein encoded by this gene belongs to the family of P-type primary ion transport ATPases characterized by the formation of an aspartyl phosphate intermediate during the reaction cycle. These enzymes remove bivalent calcium ions from eukaryotic cells against very large concentration gradients and play a critical role in intracellular calcium homeostasis. The mammalian plasma membrane calcium ATPase isoforms are encoded by at least four separate genes and the diversity of these enzymes is further increased by alternative splicing of transcripts. The expression of different isoforms and splice variants is regulated in a developmental, tissue- and cell type-specific manner, suggesting that these pumps are functionally adapted to the physiological needs of particular cells and tissues. This gene encodes the plasma membrane calcium ATPase isoform 1. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]
ATP2B1 Gene-Disease associations (from GenCC):
  • intellectual developmental disorder, autosomal dominant 66
    Inheritance: AR, AD Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ATP2B1NM_001366521.1 linkc.-222+11506T>C intron_variant Intron 1 of 20 ENST00000428670.8 NP_001353450.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ATP2B1ENST00000428670.8 linkc.-222+11506T>C intron_variant Intron 1 of 20 5 NM_001366521.1 ENSP00000392043.3 P20020-3
ATP2B1ENST00000359142.8 linkc.-222+11506T>C intron_variant Intron 1 of 21 5 ENSP00000352054.3 P20020-2
ATP2B1ENST00000551310.2 linkc.-222+12129T>C intron_variant Intron 1 of 21 3 ENSP00000447041.2 P20020-2F8W1V5
ATP2B1ENST00000705822.1 linkc.-222+12129T>C intron_variant Intron 1 of 21 ENSP00000516172.1 P20020-5

Frequencies

GnomAD3 genomes
AF:
0.152
AC:
22550
AN:
148236
Hom.:
2072
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.113
Gnomad AMI
AF:
0.0651
Gnomad AMR
AF:
0.124
Gnomad ASJ
AF:
0.237
Gnomad EAS
AF:
0.326
Gnomad SAS
AF:
0.345
Gnomad FIN
AF:
0.0706
Gnomad MID
AF:
0.232
Gnomad NFE
AF:
0.163
Gnomad OTH
AF:
0.164
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.152
AC:
22545
AN:
148298
Hom.:
2077
Cov.:
29
AF XY:
0.153
AC XY:
11044
AN XY:
72148
show subpopulations
African (AFR)
AF:
0.113
AC:
4590
AN:
40510
American (AMR)
AF:
0.124
AC:
1847
AN:
14882
Ashkenazi Jewish (ASJ)
AF:
0.237
AC:
816
AN:
3446
East Asian (EAS)
AF:
0.326
AC:
1635
AN:
5014
South Asian (SAS)
AF:
0.344
AC:
1612
AN:
4684
European-Finnish (FIN)
AF:
0.0706
AC:
657
AN:
9308
Middle Eastern (MID)
AF:
0.239
AC:
67
AN:
280
European-Non Finnish (NFE)
AF:
0.163
AC:
10928
AN:
67210
Other (OTH)
AF:
0.162
AC:
334
AN:
2058
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.498
Heterozygous variant carriers
0
885
1770
2655
3540
4425
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
268
536
804
1072
1340
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.146
Hom.:
789
Bravo
AF:
0.152
Asia WGS
AF:
0.247
AC:
861
AN:
3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
4.5
DANN
Benign
0.65
PhyloP100
0.11
Mutation Taster
=100/0
polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs12230074; hg19: chr12-90090867; API