rs4494482

chr15-49859969-T-Achr15-49859969-T-G

Variant summary

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

The NM_024837.4(ATP8B4):c.*225A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 478,878 control chromosomes in the GnomAD database, including 16,169 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 0.26 (5127 hom., cov: 32)
  • Exomes 𝑓: 0.24 (11042 hom.)
• Consequence: ATP8B4 NM_024837.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.489

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP8B4	NM_024837.4	c.*225A>T		3_prime_UTR_variant	28/28	ENST00000284509.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP8B4	ENST00000284509.11	c.*225A>T		3_prime_UTR_variant	28/28	5	NM_024837.4	P1

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38618 AN: 151030 Hom.: 5118 Cov.: 32

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.0417

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.279

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.260

GnomAD4 exome AF: 0.243 AC: 79668 AN: 327752 Hom.: 11042 Cov.: 4 AF XY: 0.244 AC XY: 40921 AN XY: 167876

Gnomad4 AFR exome AF: 0.254

Gnomad4 AMR exome AF: 0.179

Gnomad4 ASJ exome AF: 0.242

Gnomad4 EAS exome AF: 0.0149

Gnomad4 SAS exome AF: 0.228

Gnomad4 FIN exome AF: 0.266

Gnomad4 NFE exome AF: 0.271

Gnomad4 OTH exome AF: 0.253

GnomAD4 genome AF: 0.256 AC: 38653 AN: 151126 Hom.: 5127 Cov.: 32 AF XY: 0.251 AC XY: 18520 AN XY: 73760

Gnomad4 AFR AF: 0.263

Gnomad4 AMR AF: 0.214

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.0414

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.260

Gnomad4 NFE AF: 0.278

Gnomad4 OTH AF: 0.257

Alfa AF: 0.254 Hom.: 646

Bravo AF: 0.249

Asia WGS AF: 0.121 AC: 424 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	1.4
Dann	Benign	0.68

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: rs4494482; hg19: chr15-50152166;