15-50119643-C-T

Position:

• chr15-50119643-C-T

Variant summary

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

The XM_011522052.4(ATP8B4):​c.-354G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 151,740 control chromosomes in the GnomAD database, including 17,772 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 0.48 (17772 hom., cov: 30)
• Consequence: ATP8B4 XM_011522052.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.244

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 (NFE) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP8B4	XM_011522052.4	c.-354G>A		5_prime_UTR_variant	1/29		XP_011520354.1
ATP8B4	XM_011522047.3	c.-43+9G>A		intron_variant			XP_011520349.1
ATP8B4	XM_011522056.4	c.-42-12635G>A		intron_variant			XP_011520358.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP8B4	ENST00000558829.1	c.-42-12635G>A		intron_variant		3		ENSP00000453539

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72381 AN: 151624 Hom.: 17757 Cov.: 30

Gnomad AFR AF: 0.453

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.580

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.522

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

GnomAD4 genome AF: 0.477 AC: 72440 AN: 151740 Hom.: 17772 Cov.: 30 AF XY: 0.471 AC XY: 34931 AN XY: 74126

Gnomad4 AFR AF: 0.453

Gnomad4 AMR AF: 0.494

Gnomad4 ASJ AF: 0.631

Gnomad4 EAS AF: 0.193

Gnomad4 SAS AF: 0.451

Gnomad4 FIN AF: 0.382

Gnomad4 NFE AF: 0.517

Gnomad4 OTH AF: 0.519

Alfa AF: 0.520 Hom.: 39501

Bravo AF: 0.480

Asia WGS AF: 0.367 AC: 1276 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	1.7
DANN	Benign	0.46

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11853852; hg19: chr15-50411840;