rs10519257

Positions:

• chr15-50096724-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.28+10215T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 152,140 control chromosomes in the GnomAD database, including 3,171 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 0.19 (3171 hom., cov: 32)
• Consequence: ATP8B4 NM_024837.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.481

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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP8B4	NM_024837.4	c.28+10215T>C		intron_variant		ENST00000284509.11	NP_079113.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP8B4	ENST00000284509.11	c.28+10215T>C		intron_variant		5	NM_024837.4	ENSP00000284509	P1

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28709 AN: 152020 Hom.: 3173 Cov.: 32

Gnomad AFR AF: 0.0555

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.189 AC: 28697 AN: 152140 Hom.: 3171 Cov.: 32 AF XY: 0.190 AC XY: 14122 AN XY: 74376

Gnomad4 AFR AF: 0.0553

Gnomad4 AMR AF: 0.169

Gnomad4 ASJ AF: 0.291

Gnomad4 EAS AF: 0.262

Gnomad4 SAS AF: 0.268

Gnomad4 FIN AF: 0.251

Gnomad4 NFE AF: 0.247

Gnomad4 OTH AF: 0.197

Alfa AF: 0.233 Hom.: 2229

Bravo AF: 0.176

Asia WGS AF: 0.223 AC: 779 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.0
DANN	Benign	0.51

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: rs10519257; hg19: chr15-50388921;