chr1-203683316-A-G

Variant names:

• chr1-203683316-A-G
• rs1419114
• NM_001684.5:c.111A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001684.5(ATP2B4):​c.111A>G​(p.Ser37Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.886 in 1,614,012 control chromosomes in the GnomAD database, including 635,665 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.83 (53556 hom., cov: 32)
  • Exomes 𝑓: 0.89 (582109 hom.)
• Consequence: ATP2B4 NM_001684.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.54
• Publications: 28 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 1-203683316-A-G is Benign according to our data. Variant chr1-203683316-A-G is described in ClinVar as Benign. ClinVar VariationId is 1598820.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.54 with no splicing effect.
• 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP2B4	NM_001684.5	MANE Select	c.111A>G	p.Ser37Ser	synonymous	Exon 2 of 21	NP_001675.3
	ATP2B4	NM_001001396.3		c.111A>G	p.Ser37Ser	synonymous	Exon 2 of 22	NP_001001396.1	P23634-2
	ATP2B4	NM_001365783.2		c.111A>G	p.Ser37Ser	synonymous	Exon 2 of 21	NP_001352712.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP2B4	ENST00000357681.10	TSL:1 MANE Select	c.111A>G	p.Ser37Ser	synonymous	Exon 2 of 21	ENSP00000350310.5	P23634-6
	ATP2B4	ENST00000341360.7	TSL:1	c.111A>G	p.Ser37Ser	synonymous	Exon 2 of 22	ENSP00000340930.2	P23634-2
	ATP2B4	ENST00000890814.1		c.111A>G	p.Ser37Ser	synonymous	Exon 2 of 21	ENSP00000560873.1

Frequencies

GnomAD3 genomes AF: 0.833 AC: 126625 AN: 152042 Hom.: 53548 Cov.: 32

Gnomad AFR AF: 0.682

Gnomad AMI AF: 0.939

Gnomad AMR AF: 0.902

Gnomad ASJ AF: 0.908

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

GnomAD2 exomes AF: 0.883 AC: 221989 AN: 251452 AF XY: 0.883

Gnomad AFR exome AF: 0.674

Gnomad AMR exome AF: 0.944

Gnomad ASJ exome AF: 0.900

Gnomad EAS exome AF: 0.999

Gnomad FIN exome AF: 0.829

Gnomad NFE exome AF: 0.889

Gnomad OTH exome AF: 0.891

GnomAD4 exome AF: 0.891 AC: 1302603 AN: 1461852 Hom.: 582109 Cov.: 61 AF XY: 0.890 AC XY: 647305 AN XY: 727226

African (AFR) AF: 0.665 AC: 22263 AN: 33478

American (AMR) AF: 0.940 AC: 42054 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.900 AC: 23519 AN: 26134

East Asian (EAS) AF: 1.00 AC: 39690 AN: 39700

South Asian (SAS) AF: 0.858 AC: 74038 AN: 86252

European-Finnish (FIN) AF: 0.830 AC: 44318 AN: 53418

Middle Eastern (MID) AF: 0.891 AC: 5137 AN: 5768

European-Non Finnish (NFE) AF: 0.897 AC: 997832 AN: 1111984

Other (OTH) AF: 0.890 AC: 53752 AN: 60396

GnomAD4 genome AF: 0.832 AC: 126668 AN: 152160 Hom.: 53556 Cov.: 32 AF XY: 0.831 AC XY: 61846 AN XY: 74382

African (AFR) AF: 0.681 AC: 28231 AN: 41470

American (AMR) AF: 0.902 AC: 13795 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.908 AC: 3150 AN: 3470

East Asian (EAS) AF: 0.999 AC: 5172 AN: 5176

South Asian (SAS) AF: 0.854 AC: 4123 AN: 4826

European-Finnish (FIN) AF: 0.822 AC: 8711 AN: 10598

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

European-Non Finnish (NFE) AF: 0.890 AC: 60542 AN: 68014

Other (OTH) AF: 0.860 AC: 1819 AN: 2114

Alfa AF: 0.878 Hom.: 128617

Bravo AF: 0.835

Asia WGS AF: 0.926 AC: 3221 AN: 3478

EpiCase AF: 0.894

EpiControl AF: 0.889

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.054
DANN	Benign	0.34
PhyloP100		-3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1419114; hg19: chr1-203652444; COSMIC: COSV108174121;