15-50074713-G-A

Variant names:

• chr15-50074713-G-A
• rs2899453
• NM_024837.4:c.29-528C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024837.4(ATP8B4):​c.29-528C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 152,036 control chromosomes in the GnomAD database, including 22,657 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 0.54 (22657 hom., cov: 32)
• Consequence: ATP8B4 NM_024837.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.712
• Publications: 1 publications found

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]

ACMG classification

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 = 0.593 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP8B4	NM_024837.4	MANE Select	c.29-528C>T		intron	N/A	NP_079113.2
	ATP8B4	NR_073596.2		n.182-528C>T		intron	N/A
	ATP8B4	NR_073597.2		n.182-528C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP8B4	ENST00000284509.11	TSL:5 MANE Select	c.29-528C>T		intron	N/A	ENSP00000284509.6
	ATP8B4	ENST00000557955.5	TSL:1	n.29-528C>T		intron	N/A	ENSP00000453690.1
	ATP8B4	ENST00000558906.5	TSL:1	n.29-528C>T		intron	N/A	ENSP00000452956.1

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82690 AN: 151918 Hom.: 22644 Cov.: 32

Gnomad AFR AF: 0.600

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.606

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.561

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.539

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

GnomAD4 genome AF: 0.544 AC: 82735 AN: 152036 Hom.: 22657 Cov.: 32 AF XY: 0.547 AC XY: 40664 AN XY: 74306

African (AFR) AF: 0.599 AC: 24837 AN: 41454

American (AMR) AF: 0.570 AC: 8707 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 1653 AN: 3470

East Asian (EAS) AF: 0.606 AC: 3134 AN: 5168

South Asian (SAS) AF: 0.559 AC: 2698 AN: 4824

European-Finnish (FIN) AF: 0.561 AC: 5932 AN: 10570

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.501 AC: 34036 AN: 67956

Other (OTH) AF: 0.537 AC: 1134 AN: 2110

Alfa AF: 0.531 Hom.: 23578

Bravo AF: 0.548

Asia WGS AF: 0.566 AC: 1966 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	13
DANN	Benign	0.82
PhyloP100		0.71
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2899453; hg19: chr15-50366910;