rs1541254

Positions:

• chr1-203683012-C-G
• chr1-203683012-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001684.5(ATP2B4):​c.-194C>G 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 526,938 control chromosomes in the GnomAD database, including 200,205 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 (53348 hom., cov: 31)
  • Exomes 𝑓: 0.88 (146857 hom.)
• Consequence: ATP2B4 NM_001684.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.477

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP2B4	NM_001684.5	c.-194C>G		5_prime_UTR_variant	2/21	ENST00000357681.10
ATP2B4	NM_001001396.3	c.-194C>G		5_prime_UTR_variant	2/22
ATP2B4	NM_001365783.2	c.-194C>G		5_prime_UTR_variant	2/21
ATP2B4	NM_001365784.2	c.-194C>G		5_prime_UTR_variant	2/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP2B4	ENST00000357681.10	c.-194C>G		5_prime_UTR_variant	2/21	1	NM_001684.5	A1
ATP2B4	ENST00000341360.7	c.-194C>G		5_prime_UTR_variant	2/22	1		P4
ATP2B4	ENST00000705901.1	c.-194C>G		5_prime_UTR_variant	2/21

Frequencies

GnomAD3 genomes AF: 0.833 AC: 126207 AN: 151594 Hom.: 53340 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: 0.883 AC: 331173 AN: 375226 Hom.: 146857 Cov.: 5 AF XY: 0.883 AC XY: 171907 AN XY: 194740

Gnomad4 AFR exome AF: 0.669

Gnomad4 AMR exome AF: 0.921

Gnomad4 ASJ exome AF: 0.898

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.841

Gnomad4 FIN exome AF: 0.828

Gnomad4 NFE exome AF: 0.887

Gnomad4 OTH exome AF: 0.884

GnomAD4 genome AF: 0.832 AC: 126250 AN: 151712 Hom.: 53348 Cov.: 31 AF XY: 0.831 AC XY: 61606 AN XY: 74134

Gnomad4 AFR AF: 0.680

Gnomad4 AMR AF: 0.902

Gnomad4 ASJ AF: 0.907

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.854

Gnomad4 FIN AF: 0.822

Gnomad4 NFE AF: 0.890

Gnomad4 OTH AF: 0.860

Alfa AF: 0.805 Hom.: 2790

Bravo AF: 0.835

Asia WGS AF: 0.926 AC: 3221 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.9
DANN	Benign	0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs1541254; hg19: chr1-203652140;