rs10519257

Variant names:

• chr15-50096724-A-G
• rs10519257
• NM_024837.4:c.28+10215T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024837.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP8B4	NM_024837.4	MANE Select	c.28+10215T>C		intron	N/A	NP_079113.2
	ATP8B4	NR_073596.2		n.181+10215T>C		intron	N/A
	ATP8B4	NR_073597.2		n.181+10215T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP8B4	ENST00000284509.11	TSL:5 MANE Select	c.28+10215T>C		intron	N/A	ENSP00000284509.6	Q8TF62
	ATP8B4	ENST00000557955.5	TSL:1	n.28+10215T>C		intron	N/A	ENSP00000453690.1	H0YMP8
	ATP8B4	ENST00000558906.5	TSL:1	n.28+10215T>C		intron	N/A	ENSP00000452956.1	H0YLJ1

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

African (AFR) AF: 0.0553 AC: 2298 AN: 41540

American (AMR) AF: 0.169 AC: 2588 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 1010 AN: 3466

East Asian (EAS) AF: 0.262 AC: 1355 AN: 5174

South Asian (SAS) AF: 0.268 AC: 1295 AN: 4826

European-Finnish (FIN) AF: 0.251 AC: 2654 AN: 10572

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.247 AC: 16779 AN: 67964

Other (OTH) AF: 0.197 AC: 417 AN: 2112

Alfa AF: 0.233 Hom.: 2450

Bravo AF: 0.176

Asia WGS AF: 0.223 AC: 779 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.0
DANN	Benign	0.51
PhyloP100		-0.48
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10519257; hg19: chr15-50388921;