rs10519251

Variant names:

• chr15-49977476-G-A
• rs10519251
• NM_024837.4:c.1034+2141C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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=-0.89).
• 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 rank	MANE	Protein	UniProt
ATP8B4	NM_024837.4	c.1034+2141C>T		intron_variant	Intron 12 of 27	ENST00000284509.11	NP_079113.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP8B4	ENST00000284509.11	c.1034+2141C>T		intron_variant	Intron 12 of 27	5	NM_024837.4	ENSP00000284509.6

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

African (AFR) AF: 0.188 AC: 7801 AN: 41420

American (AMR) AF: 0.130 AC: 1989 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 721 AN: 3468

East Asian (EAS) AF: 0.0359 AC: 186 AN: 5174

South Asian (SAS) AF: 0.154 AC: 739 AN: 4814

European-Finnish (FIN) AF: 0.0602 AC: 638 AN: 10594

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.126 AC: 8540 AN: 67950

Other (OTH) AF: 0.157 AC: 330 AN: 2102

Alfa AF: 0.142 Hom.: 2029

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
PhyloP100		-0.028
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: rs10519251; hg19: chr15-50269673;