NM_001366521.1:c.-221-19392A>C

Variant names:

• chr12-89675499-T-G
• rs11105364
• NM_001366521.1:c.-221-19392A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001366521.1(ATP2B1):​c.-221-19392A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 152,204 control chromosomes in the GnomAD database, including 2,092 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 (2092 hom., cov: 32)
• Consequence: ATP2B1 NM_001366521.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43
• Publications: 20 publications found

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: AD, AR Classification: STRONG, MODERATE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366521.1. 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
	ATP2B1	NM_001366521.1	MANE Select	c.-221-19392A>C		intron	N/A	NP_001353450.1	P20020-3
	ATP2B1	NM_001366524.1		c.-221-19392A>C		intron	N/A	NP_001353453.1	P20020-4
	ATP2B1	NM_001366525.1		c.-221-19392A>C		intron	N/A	NP_001353454.1	P20020-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP2B1	ENST00000428670.8	TSL:5 MANE Select	c.-221-19392A>C		intron	N/A	ENSP00000392043.3	P20020-3
	ATP2B1	ENST00000960959.1		c.-221-19392A>C		intron	N/A	ENSP00000631018.1
	ATP2B1	ENST00000960960.1		c.-221-19392A>C		intron	N/A	ENSP00000631019.1

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22899 AN: 152086 Hom.: 2086 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.0648

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.0773

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.163

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

GnomAD4 genome AF: 0.150 AC: 22904 AN: 152204 Hom.: 2092 Cov.: 32 AF XY: 0.152 AC XY: 11343 AN XY: 74450

African (AFR) AF: 0.104 AC: 4328 AN: 41518

American (AMR) AF: 0.123 AC: 1885 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 827 AN: 3472

East Asian (EAS) AF: 0.329 AC: 1705 AN: 5176

South Asian (SAS) AF: 0.357 AC: 1725 AN: 4826

European-Finnish (FIN) AF: 0.0773 AC: 820 AN: 10610

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.164 AC: 11138 AN: 68002

Other (OTH) AF: 0.162 AC: 343 AN: 2116

Alfa AF: 0.140 Hom.: 405

Bravo AF: 0.149

Asia WGS AF: 0.260 AC: 907 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	12
DANN	Benign	0.40
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs11105364; hg19: chr12-90069276;