Genetic Variant NM_024837.4:c.2698-191G>A (chr15-49879650-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_024837.4(ATP8B4):c.2698-191G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 539,480 control chromosomes in the GnomAD database, including 7,021 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 0.15 ( 1836 hom., cov: 31)

Exomes 𝑓: 0.16 ( 5185 hom. )

Consequence

ATP8B4
NM_024837.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.719

Publications

3 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:

ENSG00000259188 (HGNC:):

ENSG00000259188 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=-0.89).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.251 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.2698-191G>A	intron	N/A	NP_079113.2
ATP8B4	NR_073596.2		n.2750-191G>A	intron	N/A
ATP8B4	NR_073597.2		n.2703-191G>A	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ATP8B4	ENST00000284509.11	TSL:5 MANE Select	c.2698-191G>A	intron	N/A	ENSP00000284509.6
ATP8B4	ENST00000557955.5	TSL:1	n.*396-191G>A	intron	N/A	ENSP00000453690.1
ATP8B4	ENST00000558906.5	TSL:1	n.*2228-191G>A	intron	N/A	ENSP00000452956.1

Frequencies

GnomAD3 genomes

AF:

0.152

AC:

22949

AN:

151406

Hom.:

1831

Cov.:

show subpopulations

Gnomad AFR

AF:

0.156

Gnomad AMI

AF:

0.113

Gnomad AMR

AF:

0.111

Gnomad ASJ

AF:

0.158

Gnomad EAS

AF:

0.0736

Gnomad SAS

AF:

0.263

Gnomad FIN

AF:

0.137

Gnomad MID

AF:

0.0796

Gnomad NFE

AF:

0.159

Gnomad OTH

AF:

0.145

GnomAD4 exome

AF:

0.156

AC:

60600

AN:

387956

Hom.:

5185

Cov.:

AF XY:

0.161

AC XY:

32869

AN XY:

204500

show subpopulations

African (AFR)

AF:

0.155

AC:

1504

AN:

9706

American (AMR)

AF:

0.103

AC:

1332

AN:

12938

Ashkenazi Jewish (ASJ)

AF:

0.148

AC:

1780

AN:

12036

East Asian (EAS)

AF:

0.0435

AC:

1137

AN:

26154

South Asian (SAS)

AF:

0.253

AC:

8761

AN:

34674

European-Finnish (FIN)

AF:

0.153

AC:

4896

AN:

32018

Middle Eastern (MID)

AF:

0.110

AC:

188

AN:

1712

European-Non Finnish (NFE)

AF:

0.159

AC:

37557

AN:

236486

Other (OTH)

AF:

0.155

AC:

3445

AN:

22232

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

2342

4684

7025

9367

11709

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

228

456

684

912

1140

<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:

0.152

AC:

22973

AN:

151524

Hom.:

1836

Cov.:

AF XY:

0.152

AC XY:

11231

AN XY:

74028

show subpopulations

African (AFR)

AF:

0.156

AC:

6416

AN:

41236

American (AMR)

AF:

0.111

AC:

1682

AN:

15186

Ashkenazi Jewish (ASJ)

AF:

0.158

AC:

546

AN:

3462

East Asian (EAS)

AF:

0.0738

AC:

381

AN:

5166

South Asian (SAS)

AF:

0.263

AC:

1258

AN:

4784

European-Finnish (FIN)

AF:

0.137

AC:

1435

AN:

10500

Middle Eastern (MID)

AF:

0.0822

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.159

AC:

10813

AN:

67888

Other (OTH)

AF:

0.150

AC:

315

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

940

1881

2821

3762

4702

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

270

540

810

1080

1350

<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:

0.154

Hom.:

2817

Bravo

AF:

0.145

Asia WGS

AF:

0.232

AC:

805

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.66

(source)

DANN

Benign

0.55

PhyloP100

-0.72

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