15-49920588-G-A

Variant names:

• chr15-49920588-G-A
• rs4426299
• NM_024837.4:c.1759-178C>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.1759-178C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 152,106 control chromosomes in the GnomAD database, including 5,626 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 0.23 (5626 hom., cov: 32)
• Consequence: ATP8B4 NM_024837.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.356
• Publications: 0 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.451 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.1759-178C>T		intron	N/A	NP_079113.2
	ATP8B4	NR_073596.2		n.1811-178C>T		intron	N/A
	ATP8B4	NR_073597.2		n.1912-178C>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.1759-178C>T		intron	N/A	ENSP00000284509.6
	ATP8B4	ENST00000557955.5	TSL:1	n.1759-178C>T		intron	N/A	ENSP00000453690.1
	ATP8B4	ENST00000558906.5	TSL:1	n.*1289-178C>T		intron	N/A	ENSP00000452956.1

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34567 AN: 151988 Hom.: 5623 Cov.: 32

Gnomad AFR AF: 0.456

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.0949

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.228 AC: 34610 AN: 152106 Hom.: 5626 Cov.: 32 AF XY: 0.220 AC XY: 16332 AN XY: 74368

African (AFR) AF: 0.456 AC: 18908 AN: 41446

American (AMR) AF: 0.145 AC: 2224 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 556 AN: 3470

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5180

South Asian (SAS) AF: 0.125 AC: 602 AN: 4820

European-Finnish (FIN) AF: 0.0949 AC: 1005 AN: 10590

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.156 AC: 10611 AN: 67992

Other (OTH) AF: 0.188 AC: 397 AN: 2114

Alfa AF: 0.211 Hom.: 568

Bravo AF: 0.240

Asia WGS AF: 0.0770 AC: 266 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.3
DANN	Benign	0.32
PhyloP100		0.36
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: rs4426299; hg19: chr15-50212785;