Genetic Variant ATP8B2:c.2779-143G>A (chr1-154346088-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001370597.1(ATP8B2):c.2779-143G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 1,252,374 control chromosomes in the GnomAD database, including 132,874 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 0.39 ( 13315 hom., cov: 31)

Exomes 𝑓: 0.46 ( 119559 hom. )

Consequence

ATP8B2
NM_001370597.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.923

Publications

6 publications found

Variant links:

Genes affected

ATP8B2 (HGNC:13534): (ATPase phospholipid transporting 8B2) The protein encoded by this gene belongs to the family of P-type cation transport ATPases, and to the subfamily of aminophospholipid-transporting ATPases. The aminophospholipid translocases transport phosphatidylserine and phosphatidylethanolamine from one side of a bilayer to another. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ATP8B2 links:

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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=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370597.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ATP8B2	NM_001370597.1	MANE Select	c.2779-143G>A	intron	N/A	NP_001357526.1
ATP8B2	NM_001367934.1		c.2836-143G>A	intron	N/A	NP_001354863.1
ATP8B2	NM_001370596.1		c.2782-143G>A	intron	N/A	NP_001357525.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ATP8B2	ENST00000368489.6	TSL:1 MANE Select	c.2779-143G>A	intron	N/A	ENSP00000357475.4
ATP8B2	ENST00000672630.1		c.2878-143G>A	intron	N/A	ENSP00000500034.1
ATP8B2	ENST00000696573.1		c.2836-143G>A	intron	N/A	ENSP00000512728.1

Frequencies

GnomAD3 genomes

AF:

0.393

AC:

59657

AN:

151858

Hom.:

13316

Cov.:

show subpopulations

Gnomad AFR

AF:

0.169

Gnomad AMI

AF:

0.489

Gnomad AMR

AF:

0.490

Gnomad ASJ

AF:

0.602

Gnomad EAS

AF:

0.607

Gnomad SAS

AF:

0.519

Gnomad FIN

AF:

0.419

Gnomad MID

AF:

0.491

Gnomad NFE

AF:

0.464

Gnomad OTH

AF:

0.447

GnomAD4 exome

AF:

0.461

AC:

506830

AN:

1100398

Hom.:

119559

AF XY:

0.463

AC XY:

255724

AN XY:

552094

show subpopulations

African (AFR)

AF:

0.159

AC:

4050

AN:

25544

American (AMR)

AF:

0.508

AC:

16936

AN:

33330

Ashkenazi Jewish (ASJ)

AF:

0.582

AC:

11117

AN:

19090

East Asian (EAS)

AF:

0.602

AC:

22729

AN:

37770

South Asian (SAS)

AF:

0.492

AC:

33121

AN:

67280

European-Finnish (FIN)

AF:

0.429

AC:

20548

AN:

47912

Middle Eastern (MID)

AF:

0.507

AC:

1639

AN:

3232

European-Non Finnish (NFE)

AF:

0.458

AC:

374770

AN:

818618

Other (OTH)

AF:

0.460

AC:

21920

AN:

47622

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

13775

27550

41326

55101

68876

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10234

20468

30702

40936

51170

<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:

0.393

AC:

59676

AN:

151976

Hom.:

13315

Cov.:

AF XY:

0.395

AC XY:

29339

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.169

AC:

7021

AN:

41466

American (AMR)

AF:

0.491

AC:

7499

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.602

AC:

2088

AN:

3470

East Asian (EAS)

AF:

0.608

AC:

3137

AN:

5162

South Asian (SAS)

AF:

0.520

AC:

2498

AN:

4808

European-Finnish (FIN)

AF:

0.419

AC:

4421

AN:

10540

Middle Eastern (MID)

AF:

0.476

AC:

140

AN:

294

European-Non Finnish (NFE)

AF:

0.464

AC:

31496

AN:

67938

Other (OTH)

AF:

0.441

AC:

931

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1708

3416

5124

6832

8540

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

576

1152

1728

2304

2880

<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:

0.434

Hom.:

9071

Bravo

AF:

0.391

Asia WGS

AF:

0.520

AC:

1808

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

5.3

(source)

DANN

Benign

0.20

PhyloP100

0.92

Mutation Taster

=100/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over