15-49871657-A-G

Variant summary

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

The NM_024837.4(ATP8B4):c.3027+4621T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 151,998 control chromosomes in the GnomAD database, including 7,998 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 0.31 (7998 hom., cov: 32)
• Consequence: ATP8B4 NM_024837.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.387

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 = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP8B4	NM_024837.4	c.3027+4621T>C		intron_variant		ENST00000284509.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP8B4	ENST00000284509.11	c.3027+4621T>C		intron_variant		5	NM_024837.4	P1

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46960 AN: 151880 Hom.: 7965 Cov.: 32

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.0442

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.295

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

GnomAD4 genome AF: 0.309 AC: 47040 AN: 151998 Hom.: 7998 Cov.: 32 AF XY: 0.302 AC XY: 22453 AN XY: 74278

Gnomad4 AFR AF: 0.439

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.245

Gnomad4 EAS AF: 0.0440

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.256

Gnomad4 NFE AF: 0.286

Gnomad4 OTH AF: 0.291

Alfa AF: 0.260 Hom.: 2482

Bravo AF: 0.311

Asia WGS AF: 0.139 AC: 487 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	5.7
Dann	Benign	0.85

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: rs8041979; hg19: chr15-50163854;