chr1-203682799-T-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001684.5(ATP2B4):​c.-407T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP2B4	NM_001684.5	c.-407T>A		5_prime_UTR_variant	Exon 2 of 21	ENST00000357681.10	NP_001675.3
ATP2B4	NM_001001396.3	c.-407T>A		5_prime_UTR_variant	Exon 2 of 22		NP_001001396.1
ATP2B4	NM_001365783.2	c.-407T>A		5_prime_UTR_variant	Exon 2 of 21		NP_001352712.1
ATP2B4	NM_001365784.2	c.-407T>A		5_prime_UTR_variant	Exon 2 of 21		NP_001352713.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP2B4	ENST00000357681.10	c.-407T>A		5_prime_UTR_variant	Exon 2 of 21	1	NM_001684.5	ENSP00000350310.5
ATP2B4	ENST00000341360.7	c.-407T>A		5_prime_UTR_variant	Exon 2 of 22	1		ENSP00000340930.2
ATP2B4	ENST00000705901.1	c.-407T>A		5_prime_UTR_variant	Exon 2 of 21			ENSP00000516177.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 4080 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2042

African (AFR) AF: 0.00 AC: 0 AN: 182

American (AMR) AF: 0.00 AC: 0 AN: 156

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 152

East Asian (EAS) AF: 0.00 AC: 0 AN: 148

South Asian (SAS) AF: 0.00 AC: 0 AN: 206

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 126

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 10

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2824

Other (OTH) AF: 0.00 AC: 0 AN: 276

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 118965

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	11
DANN	Benign	0.70
PhyloP100		1.1
PromoterAI		0.022	Neutral

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;