15-49905459-A-G

Variant names:

• chr15-49905459-A-G
• rs8023809
• NM_024837.4:c.2142-4220T>C

Variant summary

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

The NM_024837.4(ATP8B4):​c.2142-4220T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.773 in 152,056 control chromosomes in the GnomAD database, including 45,859 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 0.77 (45859 hom., cov: 31)
• Consequence: ATP8B4 NM_024837.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47
• Publications: 3 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.838 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP8B4	NM_024837.4	MANE Select	c.2142-4220T>C		intron	N/A	NP_079113.2
	ATP8B4	NR_073596.2		n.2194-4220T>C		intron	N/A
	ATP8B4	NR_073597.2		n.2295-7208T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP8B4	ENST00000284509.11	TSL:5 MANE Select	c.2142-4220T>C		intron	N/A	ENSP00000284509.6	Q8TF62
	ATP8B4	ENST00000557955.5	TSL:1	n.2142-7208T>C		intron	N/A	ENSP00000453690.1	H0YMP8
	ATP8B4	ENST00000558906.5	TSL:1	n.*1672-4220T>C		intron	N/A	ENSP00000452956.1	H0YLJ1

Frequencies

GnomAD3 genomes AF: 0.773 AC: 117473 AN: 151938 Hom.: 45835 Cov.: 31

Gnomad AFR AF: 0.846

Gnomad AMI AF: 0.773

Gnomad AMR AF: 0.660

Gnomad ASJ AF: 0.732

Gnomad EAS AF: 0.583

Gnomad SAS AF: 0.661

Gnomad FIN AF: 0.826

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.772

Gnomad OTH AF: 0.737

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

GnomAD4 genome AF: 0.773 AC: 117549 AN: 152056 Hom.: 45859 Cov.: 31 AF XY: 0.771 AC XY: 57249 AN XY: 74300

African (AFR) AF: 0.846 AC: 35111 AN: 41514

American (AMR) AF: 0.659 AC: 10070 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.732 AC: 2539 AN: 3468

East Asian (EAS) AF: 0.583 AC: 3006 AN: 5160

South Asian (SAS) AF: 0.661 AC: 3175 AN: 4806

European-Finnish (FIN) AF: 0.826 AC: 8737 AN: 10580

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.772 AC: 52440 AN: 67940

Other (OTH) AF: 0.734 AC: 1544 AN: 2104

Alfa AF: 0.769 Hom.: 97241

Bravo AF: 0.765

Asia WGS AF: 0.619 AC: 2159 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.25
DANN	Benign	0.62
PhyloP100		-1.5
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: rs8023809; hg19: chr15-50197656;