rs10519249

Positions:

• chr15-49976173-G-A
• chr15-49976173-G-T

Variant summary

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

The NM_024837.4(ATP8B4):​c.1035-3383C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 151,790 control chromosomes in the GnomAD database, including 23,762 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 0.53 (23762 hom., cov: 31)
• Consequence: ATP8B4 NM_024837.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09

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]

ATP8B4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.787 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP8B4	NM_024837.4	c.1035-3383C>T		intron_variant		ENST00000284509.11	NP_079113.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP8B4	ENST00000284509.11	c.1035-3383C>T		intron_variant		5	NM_024837.4	ENSP00000284509.6

Frequencies

GnomAD3 genomes AF: 0.528 AC: 80089 AN: 151672 Hom.: 23706 Cov.: 31

Gnomad AFR AF: 0.794

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.539

Gnomad ASJ AF: 0.508

Gnomad EAS AF: 0.653

Gnomad SAS AF: 0.596

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.536

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

GnomAD4 genome AF: 0.528 AC: 80209 AN: 151790 Hom.: 23762 Cov.: 31 AF XY: 0.525 AC XY: 38893 AN XY: 74128

Gnomad4 AFR AF: 0.794

Gnomad4 AMR AF: 0.540

Gnomad4 ASJ AF: 0.508

Gnomad4 EAS AF: 0.653

Gnomad4 SAS AF: 0.595

Gnomad4 FIN AF: 0.259

Gnomad4 NFE AF: 0.395

Gnomad4 OTH AF: 0.541

Alfa AF: 0.438 Hom.: 7251

Bravo AF: 0.559

Asia WGS AF: 0.664 AC: 2305 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.3
DANN	Benign	0.16

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: rs10519249; hg19: chr15-50268370;