rs12912519

Positions:

• chr15-50141323-T-G

Variant summary

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

The ENST00000558829.1(ATP8B4):​c.-42-34315A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 151,476 control chromosomes in the GnomAD database, including 5,662 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 0.25 (5662 hom., cov: 30)
• Consequence: ATP8B4 ENST00000558829.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.42

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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP8B4	XM_011522056.4	c.-42-34315A>C		intron_variant			XP_011520358.3
ATP8B4	XM_017022587.3	c.-42-34315A>C		intron_variant			XP_016878076.2
ATP8B4	XM_047433096.1	c.-42-34315A>C		intron_variant			XP_047289052.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP8B4	ENST00000558829.1	c.-42-34315A>C		intron_variant		3		ENSP00000453539

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38479 AN: 151358 Hom.: 5661 Cov.: 30

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.0352

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.260

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

GnomAD4 genome AF: 0.254 AC: 38498 AN: 151476 Hom.: 5662 Cov.: 30 AF XY: 0.256 AC XY: 18925 AN XY: 73956

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.247

Gnomad4 ASJ AF: 0.349

Gnomad4 EAS AF: 0.0357

Gnomad4 SAS AF: 0.200

Gnomad4 FIN AF: 0.372

Gnomad4 NFE AF: 0.328

Gnomad4 OTH AF: 0.257

Alfa AF: 0.313 Hom.: 7136

Bravo AF: 0.235

Asia WGS AF: 0.115 AC: 401 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.0040
DANN	Benign	0.75

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12912519; hg19: chr15-50433520;