rs10519251

Positions:

• chr15-49977476-G-A

Variant summary

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

The NM_024837.4(ATP8B4):​c.1034+2141C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 151,978 control chromosomes in the GnomAD database, including 1,631 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 0.14 (1631 hom., cov: 32)
• Consequence: ATP8B4 NM_024837.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0280

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP8B4	NM_024837.4	c.1034+2141C>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.1034+2141C>T		intron_variant		5	NM_024837.4	ENSP00000284509	P1

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21109 AN: 151860 Hom.: 1624 Cov.: 32

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.0361

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.0602

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.139 AC: 21133 AN: 151978 Hom.: 1631 Cov.: 32 AF XY: 0.137 AC XY: 10175 AN XY: 74284

Gnomad4 AFR AF: 0.188

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.208

Gnomad4 EAS AF: 0.0359

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.0602

Gnomad4 NFE AF: 0.126

Gnomad4 OTH AF: 0.157

Alfa AF: 0.142 Hom.: 1381

Bravo AF: 0.146

Asia WGS AF: 0.0980 AC: 343 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8
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: rs10519251; hg19: chr15-50269673;