15-50141503-T-C

Position:

• chr15-50141503-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000558829.1(ATP8B4):​c.-42-34495A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 151,902 control chromosomes in the GnomAD database, including 5,539 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 0.25 (5539 hom., cov: 31)
• Consequence: ATP8B4 ENST00000558829.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0490

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP8B4	XM_011522056.4	c.-42-34495A>G		intron_variant
ATP8B4	XM_017022587.3	c.-42-34495A>G		intron_variant
ATP8B4	XM_047433096.1	c.-42-34495A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP8B4	ENST00000558829.1	c.-42-34495A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38685 AN: 151782 Hom.: 5532 Cov.: 31

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.0915

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.150

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.212

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

GnomAD4 genome AF: 0.255 AC: 38729 AN: 151902 Hom.: 5539 Cov.: 31 AF XY: 0.262 AC XY: 19427 AN XY: 74254

Gnomad4 AFR AF: 0.344

Gnomad4 AMR AF: 0.267

Gnomad4 ASJ AF: 0.0915

Gnomad4 EAS AF: 0.484

Gnomad4 SAS AF: 0.349

Gnomad4 FIN AF: 0.255

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.217

Alfa AF: 0.185 Hom.: 3802

Bravo AF: 0.262

Asia WGS AF: 0.456 AC: 1578 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.5
DANN	Benign	0.26

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4774557; hg19: chr15-50433700;