15-50018951-A-G

Variant summary

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

The NM_024837.4(ATP8B4):c.363-8034T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 1,225,298 control chromosomes in the GnomAD database, including 212,770 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 0.68 (37561 hom., cov: 32)
  • Exomes 𝑓: 0.56 (175209 hom.)
• Consequence: ATP8B4 NM_024837.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.180

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP8B4	NM_024837.4	c.363-8034T>C		intron_variant		ENST00000284509.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP8B4	ENST00000284509.11	c.363-8034T>C		intron_variant		5	NM_024837.4	P1

Frequencies

GnomAD3 genomes AF: 0.681 AC: 103457 AN: 151984 Hom.: 37485 Cov.: 32

Gnomad AFR AF: 0.912

Gnomad AMI AF: 0.684

Gnomad AMR AF: 0.667

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.781

Gnomad FIN AF: 0.563

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.543

Gnomad OTH AF: 0.628

GnomAD3 exomes AF: 0.669 AC: 85615 AN: 128010 Hom.: 30566 AF XY: 0.664 AC XY: 46585 AN XY: 70106

Gnomad AFR exome AF: 0.926

Gnomad AMR exome AF: 0.746

Gnomad ASJ exome AF: 0.452

Gnomad EAS exome AF: 0.998

Gnomad SAS exome AF: 0.773

Gnomad FIN exome AF: 0.561

Gnomad NFE exome AF: 0.532

Gnomad OTH exome AF: 0.569

GnomAD4 exome AF: 0.556 AC: 596175 AN: 1073194 Hom.: 175209 Cov.: 28 AF XY: 0.563 AC XY: 297949 AN XY: 529282

Gnomad4 AFR exome AF: 0.931

Gnomad4 AMR exome AF: 0.747

Gnomad4 ASJ exome AF: 0.446

Gnomad4 EAS exome AF: 0.996

Gnomad4 SAS exome AF: 0.766

Gnomad4 FIN exome AF: 0.554

Gnomad4 NFE exome AF: 0.516

Gnomad4 OTH exome AF: 0.584

GnomAD4 genome AF: 0.681 AC: 103600 AN: 152104 Hom.: 37561 Cov.: 32 AF XY: 0.686 AC XY: 50995 AN XY: 74326

Gnomad4 AFR AF: 0.912

Gnomad4 AMR AF: 0.668

Gnomad4 ASJ AF: 0.462

Gnomad4 EAS AF: 0.994

Gnomad4 SAS AF: 0.780

Gnomad4 FIN AF: 0.563

Gnomad4 NFE AF: 0.543

Gnomad4 OTH AF: 0.632

Alfa AF: 0.588 Hom.: 4917

Bravo AF: 0.696

Asia WGS AF: 0.902 AC: 3127 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	9.5
Dann	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs11070741; hg19: chr15-50311148;