dbSNP rs8034382: ATP8B4:c.838-75T>C (chr15-49979888-A-G) – 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.838-75T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 1,026,604 control chromosomes in the GnomAD database, including 56,236 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 ( 13764 hom., cov: 32)

Exomes 𝑓: 0.30 ( 42472 hom. )

Consequence

ATP8B4
NM_024837.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.63

Publications

5 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:

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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=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP8B4	NM_024837.4 link	c.838-75T>C		intron_variant	Intron 11 of 27	ENST00000284509.11	NP_079113.2	Q8TF62Q6PG43

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP8B4	ENST00000284509.11 link	c.838-75T>C		intron_variant	Intron 11 of 27	5	NM_024837.4	ENSP00000284509.6		Q8TF62

Frequencies

GnomAD3 genomes

AF:

0.395

AC:

60009

AN:

151914

Hom.:

13753

Cov.:

show subpopulations

Gnomad AFR

AF:

0.643

Gnomad AMI

AF:

0.462

Gnomad AMR

AF:

0.305

Gnomad ASJ

AF:

0.198

Gnomad EAS

AF:

0.349

Gnomad SAS

AF:

0.306

Gnomad FIN

AF:

0.363

Gnomad MID

AF:

0.234

Gnomad NFE

AF:

0.291

Gnomad OTH

AF:

0.328

GnomAD4 exome

AF:

0.305

AC:

266461

AN:

874572

Hom.:

42472

AF XY:

0.305

AC XY:

133483

AN XY:

437680

show subpopulations

African (AFR)

AF:

0.664

AC:

14283

AN:

21506

American (AMR)

AF:

0.302

AC:

7875

AN:

26068

Ashkenazi Jewish (ASJ)

AF:

0.193

AC:

3003

AN:

15582

East Asian (EAS)

AF:

0.361

AC:

12859

AN:

35582

South Asian (SAS)

AF:

0.314

AC:

13252

AN:

42140

European-Finnish (FIN)

AF:

0.349

AC:

12809

AN:

36656

Middle Eastern (MID)

AF:

0.212

AC:

880

AN:

4158

European-Non Finnish (NFE)

AF:

0.290

AC:

189873

AN:

654386

Other (OTH)

AF:

0.302

AC:

11627

AN:

38494

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

8788

17576

26364

35152

43940

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5948

11896

17844

23792

29740

<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:

0.395

AC:

60071

AN:

152032

Hom.:

13764

Cov.:

AF XY:

0.395

AC XY:

29334

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.643

AC:

26645

AN:

41446

American (AMR)

AF:

0.305

AC:

4653

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.198

AC:

686

AN:

3466

East Asian (EAS)

AF:

0.350

AC:

1813

AN:

5184

South Asian (SAS)

AF:

0.307

AC:

1480

AN:

4828

European-Finnish (FIN)

AF:

0.363

AC:

3838

AN:

10570

Middle Eastern (MID)

AF:

0.238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.291

AC:

19783

AN:

67958

Other (OTH)

AF:

0.324

AC:

685

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1660

3319

4979

6638

8298

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

548

1096

1644

2192

2740

<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:

0.322

Hom.:

26822

Bravo

AF:

0.400

Asia WGS

AF:

0.331

AC:

1153

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.026

(source)

DANN

Benign

0.20

PhyloP100

-2.6

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over