1-203708122-G-A

Variant names:

• chr1-203708122-G-A
• rs3753036
• NM_001684.5:c.1557+18G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001684.5(ATP2B4):​c.1557+18G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 1,613,430 control chromosomes in the GnomAD database, including 26,769 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1717 hom., cov: 32)
  • Exomes 𝑓: 0.18 (25052 hom.)
• Consequence: ATP2B4 NM_001684.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0250
• Publications: 9 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 1-203708122-G-A is Benign according to our data. Variant chr1-203708122-G-A is described in ClinVar as Benign. ClinVar VariationId is 1578067.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP2B4	NM_001684.5	c.1557+18G>A		intron_variant	Intron 10 of 20	ENST00000357681.10	NP_001675.3
ATP2B4	NM_001001396.3	c.1557+18G>A		intron_variant	Intron 10 of 21		NP_001001396.1
ATP2B4	NM_001365783.2	c.1557+18G>A		intron_variant	Intron 10 of 20		NP_001352712.1
ATP2B4	NM_001365784.2	c.1557+18G>A		intron_variant	Intron 10 of 20		NP_001352713.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP2B4	ENST00000357681.10	c.1557+18G>A		intron_variant	Intron 10 of 20	1	NM_001684.5	ENSP00000350310.5
ATP2B4	ENST00000341360.7	c.1557+18G>A		intron_variant	Intron 10 of 21	1		ENSP00000340930.2
ATP2B4	ENST00000705901.1	c.1521+18G>A		intron_variant	Intron 9 of 20			ENSP00000516177.1

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20677 AN: 152008 Hom.: 1724 Cov.: 32

Gnomad AFR AF: 0.0410

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.154

GnomAD2 exomes AF: 0.164 AC: 41223 AN: 250900 AF XY: 0.173

Gnomad AFR exome AF: 0.0397

Gnomad AMR exome AF: 0.0970

Gnomad ASJ exome AF: 0.175

Gnomad EAS exome AF: 0.217

Gnomad FIN exome AF: 0.131

Gnomad NFE exome AF: 0.178

Gnomad OTH exome AF: 0.163

GnomAD4 exome AF: 0.181 AC: 264025 AN: 1461304 Hom.: 25052 Cov.: 33 AF XY: 0.183 AC XY: 133283 AN XY: 726884

African (AFR) AF: 0.0366 AC: 1225 AN: 33470

American (AMR) AF: 0.103 AC: 4599 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 4423 AN: 26118

East Asian (EAS) AF: 0.224 AC: 8897 AN: 39686

South Asian (SAS) AF: 0.241 AC: 20775 AN: 86248

European-Finnish (FIN) AF: 0.132 AC: 7046 AN: 53406

Middle Eastern (MID) AF: 0.175 AC: 1009 AN: 5766

European-Non Finnish (NFE) AF: 0.185 AC: 205288 AN: 1111504

Other (OTH) AF: 0.178 AC: 10763 AN: 60388

GnomAD4 genome AF: 0.136 AC: 20664 AN: 152126 Hom.: 1717 Cov.: 32 AF XY: 0.136 AC XY: 10121 AN XY: 74350

African (AFR) AF: 0.0410 AC: 1704 AN: 41522

American (AMR) AF: 0.128 AC: 1961 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 606 AN: 3468

East Asian (EAS) AF: 0.216 AC: 1116 AN: 5176

South Asian (SAS) AF: 0.247 AC: 1192 AN: 4822

European-Finnish (FIN) AF: 0.137 AC: 1447 AN: 10564

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.179 AC: 12141 AN: 67988

Other (OTH) AF: 0.151 AC: 317 AN: 2102

Alfa AF: 0.174 Hom.: 1390

Bravo AF: 0.132

Asia WGS AF: 0.198 AC: 688 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.1
DANN	Benign	0.49
PhyloP100		-0.025
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: rs3753036; hg19: chr1-203677250; COSMIC: COSV58174385;