rs12591825

chr15-50018938-C-Achr15-50018938-C-T

Variant summary

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

The NM_024837.4(ATP8B4):c.363-8021G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 1,230,510 control chromosomes in the GnomAD database, including 158,779 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 0.58 (27071 hom., cov: 33)
  • Exomes 𝑓: 0.47 (131708 hom.)
• Consequence: ATP8B4 NM_024837.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.266

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=-0.91).
• 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.363-8021G>T		intron_variant		ENST00000284509.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP8B4	ENST00000284509.11	c.363-8021G>T		intron_variant		5	NM_024837.4	P1

Frequencies

GnomAD3 genomes AF: 0.578 AC: 87879 AN: 151948 Hom.: 27022 Cov.: 33

Gnomad AFR AF: 0.726

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.603

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.993

Gnomad SAS AF: 0.751

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.460

Gnomad OTH AF: 0.543

GnomAD3 exomes AF: 0.608 AC: 77813 AN: 127984 Hom.: 25891 AF XY: 0.605 AC XY: 42374 AN XY: 70088

Gnomad AFR exome AF: 0.725

Gnomad AMR exome AF: 0.705

Gnomad ASJ exome AF: 0.400

Gnomad EAS exome AF: 0.998

Gnomad SAS exome AF: 0.737

Gnomad FIN exome AF: 0.496

Gnomad NFE exome AF: 0.452

Gnomad OTH exome AF: 0.513

GnomAD4 exome AF: 0.475 AC: 511781 AN: 1078444 Hom.: 131708 Cov.: 28 AF XY: 0.483 AC XY: 256781 AN XY: 531492

Gnomad4 AFR exome AF: 0.731

Gnomad4 AMR exome AF: 0.706

Gnomad4 ASJ exome AF: 0.393

Gnomad4 EAS exome AF: 0.996

Gnomad4 SAS exome AF: 0.730

Gnomad4 FIN exome AF: 0.494

Gnomad4 NFE exome AF: 0.431

Gnomad4 OTH exome AF: 0.507

GnomAD4 genome AF: 0.579 AC: 87992 AN: 152066 Hom.: 27071 Cov.: 33 AF XY: 0.586 AC XY: 43584 AN XY: 74318

Gnomad4 AFR AF: 0.726

Gnomad4 AMR AF: 0.604

Gnomad4 ASJ AF: 0.406

Gnomad4 EAS AF: 0.993

Gnomad4 SAS AF: 0.750

Gnomad4 FIN AF: 0.510

Gnomad4 NFE AF: 0.461

Gnomad4 OTH AF: 0.548

Alfa AF: 0.507 Hom.: 4509

Bravo AF: 0.588

Asia WGS AF: 0.870 AC: 3017 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.3
Dann	Benign	0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs12591825; hg19: chr15-50311135; COSMIC: COSV52723174;