chr1-203682799-T-C

Variant names:

• chr1-203682799-T-C
• rs1541252
• NM_001684.5:c.-407T>C

Variant summary

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

The NM_001684.5(ATP2B4):​c.-407T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.833 in 156,190 control chromosomes in the GnomAD database, including 55,040 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 (53549 hom., cov: 32)
  • Exomes 𝑓: 0.85 (1491 hom.)
• Consequence: ATP2B4 NM_001684.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07
• Publications: 26 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=-0.81).
• 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.-407T>C		5_prime_UTR	Exon 2 of 21	NP_001675.3
	ATP2B4	NM_001001396.3		c.-407T>C		5_prime_UTR	Exon 2 of 22	NP_001001396.1
	ATP2B4	NM_001365783.2		c.-407T>C		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.-407T>C		5_prime_UTR	Exon 2 of 21	ENSP00000350310.5
	ATP2B4	ENST00000341360.7	TSL:1	c.-407T>C		5_prime_UTR	Exon 2 of 22	ENSP00000340930.2
	ATP2B4	ENST00000705901.1		c.-407T>C		5_prime_UTR	Exon 2 of 21	ENSP00000516177.1

Frequencies

GnomAD3 genomes AF: 0.833 AC: 126602 AN: 152002 Hom.: 53541 Cov.: 32

Gnomad AFR AF: 0.681

Gnomad AMI AF: 0.939

Gnomad AMR AF: 0.902

Gnomad ASJ AF: 0.907

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.856

Gnomad FIN AF: 0.823

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.890

Gnomad OTH AF: 0.859

GnomAD4 exome AF: 0.847 AC: 3449 AN: 4070 Hom.: 1491 Cov.: 0 AF XY: 0.846 AC XY: 1727 AN XY: 2042

African (AFR) AF: 0.589 AC: 106 AN: 180

American (AMR) AF: 0.844 AC: 130 AN: 154

Ashkenazi Jewish (ASJ) AF: 0.921 AC: 140 AN: 152

East Asian (EAS) AF: 1.00 AC: 148 AN: 148

South Asian (SAS) AF: 0.684 AC: 141 AN: 206

European-Finnish (FIN) AF: 0.730 AC: 92 AN: 126

Middle Eastern (MID) AF: 0.800 AC: 8 AN: 10

European-Non Finnish (NFE) AF: 0.870 AC: 2453 AN: 2818

Other (OTH) AF: 0.837 AC: 231 AN: 276

GnomAD4 genome AF: 0.833 AC: 126645 AN: 152120 Hom.: 53549 Cov.: 32 AF XY: 0.831 AC XY: 61836 AN XY: 74376

African (AFR) AF: 0.681 AC: 28225 AN: 41468

American (AMR) AF: 0.902 AC: 13801 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.907 AC: 3149 AN: 3470

East Asian (EAS) AF: 0.999 AC: 5160 AN: 5164

South Asian (SAS) AF: 0.854 AC: 4118 AN: 4820

European-Finnish (FIN) AF: 0.823 AC: 8704 AN: 10580

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

European-Non Finnish (NFE) AF: 0.890 AC: 60546 AN: 68006

Other (OTH) AF: 0.860 AC: 1817 AN: 2112

Alfa AF: 0.868 Hom.: 118965

Bravo AF: 0.834

Asia WGS AF: 0.926 AC: 3220 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	12
DANN	Benign	0.68
PhyloP100		1.1
PromoterAI		0.0035	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: rs1541252; hg19: chr1-203651927;