dbSNP rs12020712: ATP4B:c.242-376G>A (chr13-113653810-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_000705.4(ATP4B):c.242-376G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 152,234 control chromosomes in the GnomAD database, including 3,321 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 0.20 ( 3321 hom., cov: 34)

Consequence

ATP4B
NM_000705.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.31

Publications

1 publications found

Variant links:

Genes affected

ATP4B (HGNC:820): (ATPase H+/K+ transporting subunit beta) The protein encoded by this gene belongs to a family of P-type cation-transporting ATPases. The gastric H+, K+-ATPase is a heterodimer consisting of a high molecular weight catalytic alpha subunit and a smaller but heavily glycosylated beta subunit. This enzyme is a proton pump that catalyzes the hydrolysis of ATP coupled with the exchange of H(+) and K(+) ions across the plasma membrane. It is also responsible for gastric acid secretion. This gene encodes the beta subunit of the gastric H+, K+-ATPase. [provided by RefSeq, Jul 2008]

ATP4B links:

GRK1 (HGNC:10013): (G protein-coupled receptor kinase 1) This gene encodes a member of the guanine nucleotide-binding protein (G protein)-coupled receptor kinase subfamily of the Ser/Thr protein kinase family. The protein phosphorylates rhodopsin and initiates its deactivation. Defects in GRK1 are known to cause Oguchi disease 2 (also known as stationary night blindness Oguchi type-2). [provided by RefSeq, Jul 2008]

GRK1 Gene-Disease associations (from GenCC):

Oguchi disease
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
Oguchi disease-2
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P

GRK1 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=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP4B	NM_000705.4 link	c.242-376G>A		intron_variant	Intron 2 of 6	ENST00000335288.5	NP_000696.1	P51164
GRK1	XM_047430493.1 link	c.-7+5566C>T		intron_variant	Intron 1 of 6		XP_047286449.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP4B	ENST00000335288.5 link	c.242-376G>A		intron_variant	Intron 2 of 6	1	NM_000705.4	ENSP00000334216.3		P51164

Frequencies

GnomAD3 genomes

AF:

0.204

AC:

31090

AN:

152116

Hom.:

3319

Cov.:

show subpopulations

Gnomad AFR

AF:

0.204

Gnomad AMI

AF:

0.122

Gnomad AMR

AF:

0.227

Gnomad ASJ

AF:

0.138

Gnomad EAS

AF:

0.243

Gnomad SAS

AF:

0.202

Gnomad FIN

AF:

0.150

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.210

Gnomad OTH

AF:

0.209

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.204

AC:

31109

AN:

152234

Hom.:

3321

Cov.:

AF XY:

0.201

AC XY:

14944

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.204

AC:

8474

AN:

41524

American (AMR)

AF:

0.227

AC:

3468

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.138

AC:

479

AN:

3472

East Asian (EAS)

AF:

0.243

AC:

1260

AN:

5184

South Asian (SAS)

AF:

0.202

AC:

975

AN:

4822

European-Finnish (FIN)

AF:

0.150

AC:

1593

AN:

10610

Middle Eastern (MID)

AF:

0.150

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.210

AC:

14258

AN:

67998

Other (OTH)

AF:

0.211

AC:

447

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1314

2628

3941

5255

6569

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

348

696

1044

1392

1740

<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:

0.209

Hom.:

4380

Bravo

AF:

0.212

Asia WGS

AF:

0.234

AC:

813

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.2

(source)

DANN

Benign

0.45

PhyloP100

-1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over