ENST00000484746.1:n.*4177T>C

Variant names:

• chr1-203743868-T-C
• rs970
• ENST00000484746.1:n.*4177T>C

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4 BA1

The ENST00000484746.1(ATP2B4):​n.*4177T>C variant causes a non coding transcript exon change. The variant allele was found at a frequency of 0.226 in 152,436 control chromosomes in the GnomAD database, including 4,278 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 0.23 (4277 hom., cov: 32)
  • Exomes 𝑓: 0.11 (1 hom.)
• Consequence: ATP2B4 ENST00000484746.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.40
• Publications: 13 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]

ENSG00000294708 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.17).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000484746.1. 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.*4014T>C		3_prime_UTR	Exon 21 of 21	NP_001675.3
	ATP2B4	NM_001001396.3		c.*4297T>C		3_prime_UTR	Exon 22 of 22	NP_001001396.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP2B4	ENST00000484746.1	TSL:1	n.*4177T>C		non_coding_transcript_exon	Exon 4 of 4	ENSP00000433577.1
	ATP2B4	ENST00000357681.10	TSL:1 MANE Select	c.*4014T>C		3_prime_UTR	Exon 21 of 21	ENSP00000350310.5
	ATP2B4	ENST00000341360.7	TSL:1	c.*4297T>C		3_prime_UTR	Exon 22 of 22	ENSP00000340930.2

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34439 AN: 152016 Hom.: 4279 Cov.: 32

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.0989

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.268

GnomAD4 exome AF: 0.109 AC: 33 AN: 302 Hom.: 1 Cov.: 0 AF XY: 0.144 AC XY: 27 AN XY: 188

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.108 AC: 32 AN: 296

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AF: 0.250 AC: 1 AN: 4

GnomAD4 genome AF: 0.226 AC: 34456 AN: 152134 Hom.: 4277 Cov.: 32 AF XY: 0.223 AC XY: 16575 AN XY: 74392

African (AFR) AF: 0.232 AC: 9602 AN: 41476

American (AMR) AF: 0.383 AC: 5845 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 1033 AN: 3472

East Asian (EAS) AF: 0.186 AC: 965 AN: 5180

South Asian (SAS) AF: 0.195 AC: 939 AN: 4816

European-Finnish (FIN) AF: 0.0989 AC: 1050 AN: 10618

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.205 AC: 13966 AN: 67984

Other (OTH) AF: 0.267 AC: 563 AN: 2112

Alfa AF: 0.213 Hom.: 4312

Bravo AF: 0.252

Asia WGS AF: 0.221 AC: 769 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.17
CADD	Benign	16
DANN	Benign	0.91
PhyloP100		5.4
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: rs970; hg19: chr1-203712996;