rs16963067

Positions:

• chr15-49917061-T-C

Variant summary

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

The NM_024837.4(ATP8B4):​c.2036-22A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 1,606,320 control chromosomes in the GnomAD database, including 26,435 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 0.23 (5881 hom., cov: 32)
  • Exomes 𝑓: 0.16 (20554 hom.)
• Consequence: ATP8B4 NM_024837.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.869

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP8B4	NM_024837.4	c.2036-22A>G		intron_variant		ENST00000284509.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP8B4	ENST00000284509.11	c.2036-22A>G		intron_variant		5	NM_024837.4	P1

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35219 AN: 152024 Hom.: 5875 Cov.: 32

Gnomad AFR AF: 0.469

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.00192

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.0907

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.195

GnomAD3 exomes AF: 0.149 AC: 37306 AN: 250682 Hom.: 4072 AF XY: 0.146 AC XY: 19833 AN XY: 135476

Gnomad AFR exome AF: 0.478

Gnomad AMR exome AF: 0.0950

Gnomad ASJ exome AF: 0.155

Gnomad EAS exome AF: 0.00136

Gnomad SAS exome AF: 0.139

Gnomad FIN exome AF: 0.0954

Gnomad NFE exome AF: 0.154

Gnomad OTH exome AF: 0.148

GnomAD4 exome AF: 0.156 AC: 227573 AN: 1454178 Hom.: 20554 Cov.: 29 AF XY: 0.157 AC XY: 113410 AN XY: 723984

Gnomad4 AFR exome AF: 0.486

Gnomad4 AMR exome AF: 0.102

Gnomad4 ASJ exome AF: 0.148

Gnomad4 EAS exome AF: 0.00103

Gnomad4 SAS exome AF: 0.143

Gnomad4 FIN exome AF: 0.0988

Gnomad4 NFE exome AF: 0.158

Gnomad4 OTH exome AF: 0.161

GnomAD4 genome AF: 0.232 AC: 35264 AN: 152142 Hom.: 5881 Cov.: 32 AF XY: 0.224 AC XY: 16631 AN XY: 74386

Gnomad4 AFR AF: 0.469

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.162

Gnomad4 EAS AF: 0.00193

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.0907

Gnomad4 NFE AF: 0.157

Gnomad4 OTH AF: 0.192

Alfa AF: 0.190 Hom.: 646

Bravo AF: 0.246

Asia WGS AF: 0.0790 AC: 275 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.24
DANN	Benign	0.46

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: rs16963067; hg19: chr15-50209258;