NM_001366521.1:c.1130-60G>T

Variant names:

• chr12-89624457-C-A
• rs12818945
• NM_001366521.1:c.1130-60G>T

Variant summary

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

The NM_001366521.1(ATP2B1):​c.1130-60G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0531 in 1,359,474 control chromosomes in the GnomAD database, including 2,313 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 0.045 (253 hom., cov: 32)
  • Exomes 𝑓: 0.054 (2060 hom.)
• Consequence: ATP2B1 NM_001366521.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.151
• Publications: 4 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: AR, AD Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0875 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP2B1	NM_001366521.1	c.1130-60G>T		intron_variant	Intron 8 of 20	ENST00000428670.8	NP_001353450.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP2B1	ENST00000428670.8	c.1130-60G>T		intron_variant	Intron 8 of 20	5	NM_001366521.1	ENSP00000392043.3
ATP2B1	ENST00000359142.8	c.1130-60G>T		intron_variant	Intron 8 of 21	5		ENSP00000352054.3
ATP2B1	ENST00000551310.2	c.1130-60G>T		intron_variant	Intron 8 of 21	3		ENSP00000447041.2
ATP2B1	ENST00000705822.1	c.1130-60G>T		intron_variant	Intron 8 of 21			ENSP00000516172.1

Frequencies

GnomAD3 genomes AF: 0.0454 AC: 6906 AN: 152100 Hom.: 250 Cov.: 32

Gnomad AFR AF: 0.0110

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0536

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.0942

Gnomad SAS AF: 0.0532

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0527

Gnomad OTH AF: 0.0358

GnomAD4 exome AF: 0.0541 AC: 65259 AN: 1207256 Hom.: 2060 AF XY: 0.0535 AC XY: 32377 AN XY: 605008

African (AFR) AF: 0.00786 AC: 211 AN: 26850

American (AMR) AF: 0.0698 AC: 2443 AN: 35016

Ashkenazi Jewish (ASJ) AF: 0.00408 AC: 89 AN: 21822

East Asian (EAS) AF: 0.100 AC: 3711 AN: 36936

South Asian (SAS) AF: 0.0481 AC: 3384 AN: 70382

European-Finnish (FIN) AF: 0.100 AC: 4780 AN: 47570

Middle Eastern (MID) AF: 0.0116 AC: 44 AN: 3794

European-Non Finnish (NFE) AF: 0.0527 AC: 48160 AN: 913588

Other (OTH) AF: 0.0475 AC: 2437 AN: 51298

GnomAD4 genome AF: 0.0454 AC: 6916 AN: 152218 Hom.: 253 Cov.: 32 AF XY: 0.0483 AC XY: 3592 AN XY: 74424

African (AFR) AF: 0.0110 AC: 457 AN: 41544

American (AMR) AF: 0.0541 AC: 828 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00576 AC: 20 AN: 3472

East Asian (EAS) AF: 0.0944 AC: 489 AN: 5180

South Asian (SAS) AF: 0.0533 AC: 257 AN: 4826

European-Finnish (FIN) AF: 0.112 AC: 1187 AN: 10580

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0527 AC: 3585 AN: 68000

Other (OTH) AF: 0.0359 AC: 76 AN: 2116

Alfa AF: 0.0341 Hom.: 44

Bravo AF: 0.0414

Asia WGS AF: 0.0680 AC: 234 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.1
DANN	Benign	0.51
PhyloP100		-0.15
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: rs12818945; hg19: chr12-90018234;