rs970

Positions:

• chr1-203743868-T-C

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4 BA1

The NM_001684.5(ATP2B4):​c.*4014T>C variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.226 in 152,436 control chromosomes in the GnomAD database, including 4,278 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 0.23 (4277 hom., cov: 32)
  • Exomes 𝑓: 0.11 (1 hom.)
• Consequence: ATP2B4 NM_001684.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.40

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]

LOC102723543 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.17).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP2B4	NM_001684.5	c.*4014T>C		3_prime_UTR_variant	21/21	ENST00000357681.10
LOC102723543	XR_426890.4	n.355+337A>G		intron_variant, non_coding_transcript_variant
ATP2B4	NM_001001396.3	c.*4297T>C		3_prime_UTR_variant	22/22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP2B4	ENST00000357681.10	c.*4014T>C		3_prime_UTR_variant	21/21	1	NM_001684.5	A1
ATP2B4	ENST00000341360.7	c.*4297T>C		3_prime_UTR_variant	22/22	1		P4
ATP2B4	ENST00000484746.1	c.*4177T>C		3_prime_UTR_variant, NMD_transcript_variant	4/4	1

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34439 AN: 152016 Hom.: 4279 Cov.: 32

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.0989

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.268

GnomAD4 exome AF: 0.109 AC: 33 AN: 302 Hom.: 1 Cov.: 0 AF XY: 0.144 AC XY: 27 AN XY: 188

Gnomad4 FIN exome AF: 0.108

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.226 AC: 34456 AN: 152134 Hom.: 4277 Cov.: 32 AF XY: 0.223 AC XY: 16575 AN XY: 74392

Gnomad4 AFR AF: 0.232

Gnomad4 AMR AF: 0.383

Gnomad4 ASJ AF: 0.298

Gnomad4 EAS AF: 0.186

Gnomad4 SAS AF: 0.195

Gnomad4 FIN AF: 0.0989

Gnomad4 NFE AF: 0.205

Gnomad4 OTH AF: 0.267

Alfa AF: 0.210 Hom.: 3498

Bravo AF: 0.252

Asia WGS AF: 0.221 AC: 769 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.17
CADD	Benign	16
DANN	Benign	0.91

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: rs970; hg19: chr1-203712996;