Genetic Variant NM_001684.5:c.-407T>C (chr1-203682799-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.07

Publications

26 publications found

Variant links:

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]

ATP2B4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ATP2B4	NM_001684.5 link	c.-407T>C	5_prime_UTR_variant	Exon 2 of 21	ENST00000357681.10	NP_001675.3	P23634-6A0A024R968
ATP2B4	NM_001001396.3 link	c.-407T>C	5_prime_UTR_variant	Exon 2 of 22		NP_001001396.1	P23634-2
ATP2B4	NM_001365783.2 link	c.-407T>C	5_prime_UTR_variant	Exon 2 of 21		NP_001352712.1
ATP2B4	NM_001365784.2 link	c.-407T>C	5_prime_UTR_variant	Exon 2 of 21		NP_001352713.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ATP2B4	ENST00000357681.10 link	c.-407T>C	5_prime_UTR_variant	Exon 2 of 21	1	NM_001684.5	ENSP00000350310.5	P23634-6
ATP2B4	ENST00000341360.7 link	c.-407T>C	5_prime_UTR_variant	Exon 2 of 22	1		ENSP00000340930.2	P23634-2
ATP2B4	ENST00000705901.1 link	c.-407T>C	5_prime_UTR_variant	Exon 2 of 21			ENSP00000516177.1	P23634-3

Frequencies

GnomAD3 genomes

AF:

0.833

AC:

126602

AN:

152002

Hom.:

53541

Cov.:

show subpopulations

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.:

AF XY:

0.846

AC XY:

1727

AN XY:

2042

show subpopulations

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:

AN:

126

Middle Eastern (MID)

AF:

0.800

AC:

AN:

European-Non Finnish (NFE)

AF:

0.870

AC:

2453

AN:

2818

Other (OTH)

AF:

0.837

AC:

231

AN:

276

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

112

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.833

AC:

126645

AN:

152120

Hom.:

53549

Cov.:

AF XY:

0.831

AC XY:

61836

AN XY:

74376

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1016

2031

3047

4062

5078

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

880

1760

2640

3520

4400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

(source)

DANN

Benign

0.68

PhyloP100

1.1

PromoterAI

0.0035

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over