chr1-203691653-A-G

Position:

• chr1-203691653-A-G

Variant summary

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

The NM_001684.5(ATP2B4):​c.194-6504A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.837 in 152,196 control chromosomes in the GnomAD database, including 53,969 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 0.84 (53969 hom., cov: 32)
• Consequence: ATP2B4 NM_001684.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.295

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=-0.9).
• 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	Protein	UniProt
ATP2B4	NM_001684.5	c.194-6504A>G		intron_variant		ENST00000357681.10	NP_001675.3
ATP2B4	NM_001001396.3	c.194-6504A>G		intron_variant			NP_001001396.1
ATP2B4	NM_001365783.2	c.194-6504A>G		intron_variant			NP_001352712.1
ATP2B4	NM_001365784.2	c.194-6504A>G		intron_variant			NP_001352713.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP2B4	ENST00000357681.10	c.194-6504A>G		intron_variant		1	NM_001684.5	ENSP00000350310.5
ATP2B4	ENST00000341360.7	c.194-6504A>G		intron_variant		1		ENSP00000340930.2
ATP2B4	ENST00000705901.1	c.194-6504A>G		intron_variant				ENSP00000516177.1

Frequencies

GnomAD3 genomes AF: 0.837 AC: 127294 AN: 152078 Hom.: 53949 Cov.: 32

Gnomad AFR AF: 0.698

Gnomad AMI AF: 0.938

Gnomad AMR AF: 0.903

Gnomad ASJ AF: 0.878

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.856

Gnomad FIN AF: 0.827

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.890

Gnomad OTH AF: 0.864

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

GnomAD4 genome AF: 0.837 AC: 127356 AN: 152196 Hom.: 53969 Cov.: 32 AF XY: 0.837 AC XY: 62285 AN XY: 74402

Gnomad4 AFR AF: 0.697

Gnomad4 AMR AF: 0.903

Gnomad4 ASJ AF: 0.878

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.855

Gnomad4 FIN AF: 0.827

Gnomad4 NFE AF: 0.890

Gnomad4 OTH AF: 0.865

Alfa AF: 0.836 Hom.: 5149

Bravo AF: 0.840

Asia WGS AF: 0.928 AC: 3229 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.92
DANN	Benign	0.44

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: rs4951074; hg19: chr1-203660781;