Genetic Variant ATP8B4:c.2142-117C>T (chr15-49901356-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_024837.4(ATP8B4):c.2142-117C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 1,084,428 control chromosomes in the GnomAD database, including 94,047 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 0.40 ( 13255 hom., cov: 33)

Exomes 𝑓: 0.40 ( 80792 hom. )

Consequence

ATP8B4
NM_024837.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.41

Publications

8 publications found

Variant links:

Genes affected

ATP8B4 (HGNC:13536): (ATPase phospholipid transporting 8B4 (putative)) This gene encodes a member of the cation transport ATPase (P-type) family and type IV subfamily. The encoded protein is involved in phospholipid transport in the cell membrane. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2013]

ATP8B4 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=-0.66).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.836 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024837.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ATP8B4	NM_024837.4	MANE Select	c.2142-117C>T	intron	N/A	NP_079113.2
ATP8B4	NR_073596.2		n.2194-117C>T	intron	N/A
ATP8B4	NR_073597.2		n.2295-3105C>T	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ATP8B4	ENST00000284509.11	TSL:5 MANE Select	c.2142-117C>T	intron	N/A	ENSP00000284509.6
ATP8B4	ENST00000557955.5	TSL:1	n.2142-3105C>T	intron	N/A	ENSP00000453690.1
ATP8B4	ENST00000558906.5	TSL:1	n.*1672-117C>T	intron	N/A	ENSP00000452956.1

Frequencies

GnomAD3 genomes

AF:

0.402

AC:

61141

AN:

151932

Hom.:

13247

Cov.:

show subpopulations

Gnomad AFR

AF:

0.322

Gnomad AMI

AF:

0.366

Gnomad AMR

AF:

0.525

Gnomad ASJ

AF:

0.303

Gnomad EAS

AF:

0.857

Gnomad SAS

AF:

0.497

Gnomad FIN

AF:

0.477

Gnomad MID

AF:

0.326

Gnomad NFE

AF:

0.376

Gnomad OTH

AF:

0.423

GnomAD4 exome

AF:

0.401

AC:

373874

AN:

932378

Hom.:

80792

AF XY:

0.403

AC XY:

187740

AN XY:

465774

show subpopulations

African (AFR)

AF:

0.310

AC:

6503

AN:

21004

American (AMR)

AF:

0.578

AC:

11738

AN:

20318

Ashkenazi Jewish (ASJ)

AF:

0.316

AC:

5286

AN:

16712

East Asian (EAS)

AF:

0.880

AC:

29317

AN:

33332

South Asian (SAS)

AF:

0.492

AC:

25694

AN:

52212

European-Finnish (FIN)

AF:

0.463

AC:

17099

AN:

36912

Middle Eastern (MID)

AF:

0.286

AC:

955

AN:

3344

European-Non Finnish (NFE)

AF:

0.368

AC:

260267

AN:

706756

Other (OTH)

AF:

0.407

AC:

17015

AN:

41788

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

10135

20270

30404

40539

50674

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7526

15052

22578

30104

37630

<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:

0.402

AC:

61190

AN:

152050

Hom.:

13255

Cov.:

AF XY:

0.412

AC XY:

30631

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.322

AC:

13347

AN:

41484

American (AMR)

AF:

0.526

AC:

8031

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.303

AC:

1053

AN:

3470

East Asian (EAS)

AF:

0.857

AC:

4436

AN:

5178

South Asian (SAS)

AF:

0.498

AC:

2399

AN:

4822

European-Finnish (FIN)

AF:

0.477

AC:

5019

AN:

10530

Middle Eastern (MID)

AF:

0.333

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.376

AC:

25576

AN:

67968

Other (OTH)

AF:

0.424

AC:

897

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1821

3641

5462

7282

9103

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

580

1160

1740

2320

2900

<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:

0.375

Hom.:

21777

Bravo

AF:

0.400

Asia WGS

AF:

0.649

AC:

2252

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Benign

0.66

PhyloP100

1.4

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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