15-49991464-T-C

Variant names:

• chr15-49991464-T-C
• rs10519252
• NM_024837.4:c.590-3915A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024837.4(ATP8B4):​c.590-3915A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 152,144 control chromosomes in the GnomAD database, including 6,823 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 0.29 (6823 hom., cov: 33)
• Consequence: ATP8B4 NM_024837.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.937
• Publications: 2 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=-0.6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.557 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP8B4	NM_024837.4	MANE Select	c.590-3915A>G		intron	N/A	NP_079113.2
	ATP8B4	NR_073596.2		n.831-3915A>G		intron	N/A
	ATP8B4	NR_073597.2		n.743-3915A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP8B4	ENST00000284509.11	TSL:5 MANE Select	c.590-3915A>G		intron	N/A	ENSP00000284509.6
	ATP8B4	ENST00000557955.5	TSL:1	n.590-3915A>G		intron	N/A	ENSP00000453690.1
	ATP8B4	ENST00000558906.5	TSL:1	n.*309-3915A>G		intron	N/A	ENSP00000452956.1

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43840 AN: 152026 Hom.: 6805 Cov.: 33

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.574

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.318

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

GnomAD4 genome AF: 0.289 AC: 43902 AN: 152144 Hom.: 6823 Cov.: 33 AF XY: 0.294 AC XY: 21877 AN XY: 74382

African (AFR) AF: 0.212 AC: 8807 AN: 41534

American (AMR) AF: 0.385 AC: 5879 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1087 AN: 3472

East Asian (EAS) AF: 0.574 AC: 2972 AN: 5176

South Asian (SAS) AF: 0.478 AC: 2306 AN: 4828

European-Finnish (FIN) AF: 0.232 AC: 2451 AN: 10578

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.285 AC: 19343 AN: 67976

Other (OTH) AF: 0.320 AC: 677 AN: 2114

Alfa AF: 0.288 Hom.: 8722

Bravo AF: 0.295

Asia WGS AF: 0.479 AC: 1663 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	17
DANN	Benign	0.84
PhyloP100		0.94
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: rs10519252; hg19: chr15-50283661;