15-50010667-T-C

Variant names:

• chr15-50010667-T-C
• rs16963207
• NM_024837.4:c.435+178A>G

Variant summary

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

The NM_024837.4(ATP8B4):​c.435+178A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.082 in 152,174 control chromosomes in the GnomAD database, including 710 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 0.082 (710 hom., cov: 32)
• Consequence: ATP8B4 NM_024837.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.582
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.274 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.435+178A>G		intron	N/A	NP_079113.2
	ATP8B4	NR_073596.2		n.676+178A>G		intron	N/A
	ATP8B4	NR_073597.2		n.588+178A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP8B4	ENST00000284509.11	TSL:5 MANE Select	c.435+178A>G		intron	N/A	ENSP00000284509.6
	ATP8B4	ENST00000557955.5	TSL:1	n.435+178A>G		intron	N/A	ENSP00000453690.1
	ATP8B4	ENST00000558906.5	TSL:1	n.*154+178A>G		intron	N/A	ENSP00000452956.1

Frequencies

GnomAD3 genomes AF: 0.0820 AC: 12461 AN: 152054 Hom.: 710 Cov.: 32

Gnomad AFR AF: 0.0637

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.0732

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.286

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.0989

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.0663

Gnomad OTH AF: 0.0877

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

GnomAD4 genome AF: 0.0820 AC: 12478 AN: 152174 Hom.: 710 Cov.: 32 AF XY: 0.0872 AC XY: 6490 AN XY: 74396

African (AFR) AF: 0.0638 AC: 2652 AN: 41562

American (AMR) AF: 0.0733 AC: 1118 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 478 AN: 3468

East Asian (EAS) AF: 0.286 AC: 1482 AN: 5182

South Asian (SAS) AF: 0.186 AC: 896 AN: 4826

European-Finnish (FIN) AF: 0.0989 AC: 1048 AN: 10596

Middle Eastern (MID) AF: 0.195 AC: 57 AN: 292

European-Non Finnish (NFE) AF: 0.0664 AC: 4511 AN: 67966

Other (OTH) AF: 0.0916 AC: 193 AN: 2108

Alfa AF: 0.0694 Hom.: 194

Bravo AF: 0.0774

Asia WGS AF: 0.205 AC: 706 AN: 3446

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.1
DANN	Benign	0.77
PhyloP100		0.58
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: rs16963207; hg19: chr15-50302864;