1-203683013-G-A

Variant names:

• chr1-203683013-G-A
• rs1541255
• NM_001684.5:c.-193G>A

Variant summary

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

The NM_001684.5(ATP2B4):​c.-193G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.868 in 527,448 control chromosomes in the GnomAD database, including 200,323 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 0.83 (53351 hom., cov: 31)
  • Exomes 𝑓: 0.88 (146972 hom.)
• Consequence: ATP2B4 NM_001684.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.502
• Publications: 20 publications found

Genes affected

ATP2B4 (HGNC:817): (ATPase plasma membrane Ca2+ transporting 4) 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 4. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001684.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP2B4	NM_001684.5	MANE Select	c.-193G>A		5_prime_UTR	Exon 2 of 21	NP_001675.3
	ATP2B4	NM_001001396.3		c.-193G>A		5_prime_UTR	Exon 2 of 22	NP_001001396.1
	ATP2B4	NM_001365783.2		c.-193G>A		5_prime_UTR	Exon 2 of 21	NP_001352712.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP2B4	ENST00000357681.10	TSL:1 MANE Select	c.-193G>A		5_prime_UTR	Exon 2 of 21	ENSP00000350310.5
	ATP2B4	ENST00000341360.7	TSL:1	c.-193G>A		5_prime_UTR	Exon 2 of 22	ENSP00000340930.2
	ATP2B4	ENST00000705901.1		c.-193G>A		5_prime_UTR	Exon 2 of 21	ENSP00000516177.1

Frequencies

GnomAD3 genomes AF: 0.833 AC: 126208 AN: 151586 Hom.: 53343 Cov.: 31

Gnomad AFR AF: 0.681

Gnomad AMI AF: 0.938

Gnomad AMR AF: 0.902

Gnomad ASJ AF: 0.907

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.855

Gnomad FIN AF: 0.822

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.890

Gnomad OTH AF: 0.859

GnomAD4 exome AF: 0.882 AC: 331537 AN: 375744 Hom.: 146972 Cov.: 5 AF XY: 0.882 AC XY: 172068 AN XY: 194990

African (AFR) AF: 0.668 AC: 7275 AN: 10896

American (AMR) AF: 0.921 AC: 12877 AN: 13976

Ashkenazi Jewish (ASJ) AF: 0.898 AC: 10157 AN: 11312

East Asian (EAS) AF: 1.00 AC: 25851 AN: 25858

South Asian (SAS) AF: 0.841 AC: 23757 AN: 28244

European-Finnish (FIN) AF: 0.828 AC: 20782 AN: 25098

Middle Eastern (MID) AF: 0.893 AC: 1466 AN: 1642

European-Non Finnish (NFE) AF: 0.887 AC: 210042 AN: 236854

Other (OTH) AF: 0.884 AC: 19330 AN: 21864

GnomAD4 genome AF: 0.832 AC: 126251 AN: 151704 Hom.: 53351 Cov.: 31 AF XY: 0.831 AC XY: 61606 AN XY: 74132

African (AFR) AF: 0.680 AC: 28092 AN: 41322

American (AMR) AF: 0.902 AC: 13788 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.907 AC: 3145 AN: 3466

East Asian (EAS) AF: 0.999 AC: 5156 AN: 5160

South Asian (SAS) AF: 0.854 AC: 4102 AN: 4804

European-Finnish (FIN) AF: 0.822 AC: 8631 AN: 10502

Middle Eastern (MID) AF: 0.915 AC: 269 AN: 294

European-Non Finnish (NFE) AF: 0.890 AC: 60404 AN: 67860

Other (OTH) AF: 0.860 AC: 1812 AN: 2106

Alfa AF: 0.853 Hom.: 14666

Bravo AF: 0.835

Asia WGS AF: 0.926 AC: 3221 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.0
DANN	Benign	0.65
PhyloP100		-0.50
PromoterAI		-0.094	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=300/0	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: rs1541255; hg19: chr1-203652141;